Velosano 2 Annual Report

VELOSANO 2ANNUAL REPORT





Table of ContentsLiving Hope 6VeloSano 2 | By the Numbers 8VeloSano 2 | Top 10 Lists 9VeloSano 1 | Research Update 11Where The Money Goes 12Case CCC Pilot Awards 30VeloSano Partners 35Big Wheelers presented by KeyBank 36VeloSano 2 Steering Committee 37The Future of Cancer Care at Cleveland Clinic 38The Power of Every One 39

VELOSANO 2 | ANNUAL REPORT 5 Brian Bolwell, M.D. and Stewart Kohl, VeloSano Founder at the start line during VeloSano 2Thank you for being part of our VeloSano family. Our primary goal, as you are aware, is to fundcancer research, and continue to make scientific discoveries that lead to better outcomes, and,ultimately, cures. For the second year, I had the honor of overseeing the selection process for theVeloSano Pilot Awards and the designation of the VeloSano Impact Awards. The Pilot Awards arescientific proposals made by Cleveland Clinic researchers from many different specialties. Theyhave become very competitive, and this year we had over 60 applications. This required twoseparate levels of review. The first was to determine the top 30 that would be ranked, and thesecond was the actual ranking.Eighteen scientific leaders judged these applications. After significant deliberation, 15 awardswere distributed, at an amount of $100,000 per award (this is greater than the $75,000 peraward we were able to allocate last year). These awards included studying genomic mutations ina variety of cancers, including colon cancer; studying cancer stem cells and brain tumors; novelprecision therapies for leukemia; and many other outstanding projects. The dollars raised fromVeloSano are of vital importance to stimulate this extremely promising research.The VeloSano Impact Awards are granted to large-scale projects that are among our CancerInstitute’s highest priorities. Examples include using xenografts to create avatars of humancancers; studying and preventing the development of blood clots in patients with selected tumors;and establishing a novel protocol for freezing ovarian tissue to preserve fertility.Cleveland Clinic is the home of many world-renowned scientists and researchers. VeloSano isallowing us to make meaningful discoveries right now, that will translate into improved patientcare. This is a big deal. We are extraordinarily grateful for these opportunities, and we plan oncontinuing to work very hard to advance this field with the dollars raised, thanks to all of you.We will look forward to seeing you at VeloSano 3 in July. Bike to cure!Sincerely yours,Brian J. Bolwell M.D., F.A.C.P.Chairman, Taussig Cancer InstituteMedical Chairman, VeloSano

As VeloSano continues to grow, we are focused on not only Riders, Virtual Riders and Volunteers frombringing in significant funds to advance cancer research but also these special groups will be recognizedto continually enhance and evolve. as Living Hope in various ways, including on their personal fundraising pagesWith that, we are taking our former term that was specific on velosano.org and throughout eventto cancer survivors only (Living Proof), and evolving it to weekend, to name a few.incorporate both current patients and survivors. While we strive for the day when thereThat new term: Living Hope. will be no more cancer, for now, join us in honoring our Living Hope community.

VELOSANO 2 | ANNUAL REPORT 7J. Mark Brown , Ph.D.From Cancer Patient to Cancer ResearcherIn April 2013, I joined Cleveland Clinic as a basic science staffmember in the Lerner Research Institute and in August 2013 I wasunexpectedly diagnosed with stage III colon cancer. After two majorsurgeries, 6 months of intensive chemotherapy, and state of the artmedical care given at Cleveland Clinic - I am now cancer free! Beinga cancer survivor myself and experiencing the world class care that Ihave received from my colleagues at Cleveland Clinic, has ignited a newpassion for cancer research in my laboratory. My laboratory’s researchhas historically been focused on nutrient metabolism, and now weare leveraging our expertise in this area to find new cures for cancer.Proceeds from last year’s ride provided funding for my laboratory tostudy how we can treat liver cancer (hepatocellular carcinoma), and wenow have exciting findings of new potential drug to treat liver cancer.

VeloSano 2 | By the Numbers$3,000,000 raisedfor cancer research 1,300 states, DC, 3and Riders from... and Ontario countries65% 228 214 increase in Riders Riders at least doubled their minimum Virtual Riders from VS 1 to VS 2 commitment to become Big Wheelers913 147 18,000+Volunteers Living Hope Participants Gifts received from all 50 states, DC and 25 countries (cancer survivor / cancer patient community)

VELOSANO 2 | ANNUAL REPORT 9VeloSano 2 | Top 10 Lists Top 10 Fundraising Teams $301,954 1. Cleveland Clinic $210,527 2. The Riverside Company $203,652 3. Big Galoots Bicycle Club $202,291 4. Cleveland StARTup Collective $147,217 5. Taussig Cyclotrons $135,156 6. Cleveland Indians $69,010 7. Team Key $67,018 8. Jones Day $66,180 9. Cardinal Health $64,238 10. Make It Rain Top 10 Fundraising Riders $262,600 1. Marc Harrison $172,372 2. Joanne Cohen $144,655 3. Stewart Kohl $51,973 4. Paul Dolan $47,423 5. Bob Rich $28,531 6. Michelle Amato $20,000 7. John Fung $17,812 8. Hiroyuki Fujita $17,635 9. Matt Litzler $16,970 10. Larry Pollock Top 10 Fundraising Virtual Riders 1. Jorge Garcia $10,760 2. Zumi Pig $6,015 3. Peter Dougherty $3,450 4. Jaroslaw Maciejewski $3,402 5. Brian Bolwell $2,925 6. Shlomo Koyfman $2,775 7. Jenna Oliverio $2,151 8. Brian Laliberte $1,529 9. Yogen Saunthararajah $1,365 10. Eric Tischler $1,270

Why I Ride

VELOSANO 2 | ANNUAL REPORT 11 Justin Durla VELOSANO 2 RIDER Lathia, Ph.D. (left)VeloSano 1 | Research UpdateReversing Immune Cell Suppression and Enhancing When the suppressive immune cells were targeted,Cytotoxic T Cell Response in Glioblastoma by Targeting tumors did not grow as well and contain manyMyeloidderived Suppressor Cells immune cell populations that have the capacity to target and kill tumor cells. This is an attractivePrincipal Investigator: Justin Durla Lathia, Ph.D. strategy as it allows the body’s immune systemCo-Investigator: Michael Vogelbaum, M.D., Ph.D. to function to eliminate the tumor. This approach is complementary to immune-based therapiesThe immune system ensures normal tissue function by responding to injury and being currently evaluated as our approach targetsinfection to minimize damage. While the immune system is tightly regulated, suppressive immune cells while many currentin malignant tumors, such as those in the brain, its function is suppressed by therapies are attempting to increase immunethe tumor cells and the recruitment of unique immune cell populations with system function. Based on these observations, wesuppressive function. The goal of our VeloSano pilot grant was to determine are initiating a pilot clinical trial in which we willhow recruited suppressive immune cells function in brain tumors and explore track suppressive immune cells in patients afterstrategies to target them. We were able to identify a pathway that therapy- they receive 5-fluoruracil. Once we can demonstrateresistant tumor cells use to amplify the function of these suppressive immune the ability to target suppressive immune cells, wecells and this work will be published shortly in a top-tier journal, Stem Cells. are hoping to initiate a larger scale trial to lookWe also explored several ways to target these suppressive immune cells at how this strategy may be combined with otherand found that a conventional chemotherapy, 5-fluoruracil, could eliminate therapies.these cells in pre-clinical models. We found that we could effectively targetsuppressive immune cells at a dose 20-fold less than what is routinely given.

$3,000,000 Pilot AwardsYou gave 100%, so will we. The VeloSano Pilot Awards provide seed funding for cancer research activities being performed across the Cleveland Clinic enterprise. Utilizing a competitive application and peer-review selection process, the goal of the VeloSano Pilot Awards is to support projects with a high likelihood of leading to successful, future extramural grant funding. The focus of these one year grants is to build upon and transition recent advancements in cancer genetics and epigenetics and basic and translational tumor immunology. Impact Awards The VeloSano Impact Awards are distributed by the VeloSano Medical Chairman to satisfy the critical needs of the Cleveland Clinic cancer program. Whether a piece of equipment, advanced technology, recruitment or laboratory expenses, the VeloSano Impact Awards are to address strategic priorities that will advance the investigational abilities in the area of cancer research. These awards are meant to ensure that our caregivers and patients have access to the best talent and technology available.

VELOSANO 2 | ANNUAL REPORT 13(L–R)Federico Aucejo, M.D.J. Mark Brown, Ph.D.Daniela Allende, M.D.PILOT AWARDTargeting Lipid Metabolism toPrevent Hepatocellular Carcinoma ProgressionPrincipal Investigator: J. Mark Brown, Ph.D.Co-Investigators: Federico Aucejo, M.D. and Daniela Allende, M.D.Obesity represents a rapidly expanding health care burden in developed countries, and is recognized as amajor risk factor for the development of many types of cancer. In particular, hepatocellular carcinoma (HCC)-driven mortality is strikingly associated with obesity. HCC is known to be predominantly driven by hepatitisB (HBV) or hepatitis C (HCV) viral infection. However, highly effective vaccines targeting HBV and curativeanti-HCV drugs are now readily available, which will likely result in a sharp decline in viral-driven HCC overthe next decade. In contrast, the incidence of obesity-driven HCC is poised to rise at an alarming rate as theobesity epidemic continues to grow. Importantly, the molecular mechanisms linking obesity to HCC are notknown. Furthermore, animal models that recapitulate human-relevant obesity related disease progression arelacking. To address these gaps our team has established both viral- and obesity-driven mouse models of HCCthat allow us to model human-relevant disease progression. We have also begun establishing patient-derivedxenografts of obesity-driven HCC to study molecular mechanisms driving malignancy. Most importantly,we have identified a novel lipase drug target for prevention of obesity-driven HCC, and have establishedcollaborative efforts with major pharmaceutical companies to rapidly move lead compounds from bench tobedside. Significance: These studies will lay the foundation for next generation targeted therapeutics for HCC,and have broad implications for many other obesity-linked cancers.

Xiaorong Gu, Ph.D.PILOT AWARDNovel, Precision Therapy for Relapsed NPM1-Mutated AMLPrincipal Investigator: Xiaorong Gu, Ph.D.Co-Investigator: Yogen Saunthararajah, M.D.NPM1 is the most commonly mutated gene in de novo Acute Myeloid Leukemia (AML). Despite beingconsidered a more favorable risk in AML, only ~50% of patients exhibit long-term survival due to relapsethat is resistant to treatments. One reason is that current treatments intend cytotoxicity, via p53, the mastertranscription factor (TF) of apoptosis. Unfortunately, p53-system is frequently attenuated by genetic alterationsin AML, subverts this common apoptotic intent, causing resistance in vitro and clinically. Meanwhile, normalhematopoietic stem cells (HSC) with intact p53 are destroyed, causing substantial toxicities including death.Therefore, new treatments that use pathways other than p53/apoptosis for cell cycle exits are needed.Cell cycle exits by differentiation do not require p53. Myeloid differentiation is driven by only a few masterTFs, suggesting disruption of master TF function underlies differentiation-arrest. We discovered that NPM1 isa co-factor for the master TF PU.1, and in mNPM1 AML, PU.1 and NPM1 dislocated from the nucleus intothe cytoplasm. Inhibition of nuclear-cytoplasmic exporting (KPT330, CRM1-inhibition) restored both mNPM1and PU.1 into the nucleus, triggering terminal monocytic differentiation. We also discovered that mNPM1-AML appears to respond to nanomolar concentrations of retinoic acid (ATRA) with terminal granulocyticdifferentiation. Realistically, neither single agent CRM1-inhibition nor single agent ATRA will be curative. Itis possible, however, that resistance to one may increase susceptibility to the other. We will investigate themolecular mechanisms underlying differentiation-arrest and its pharmacological reversal, in order to developrational p53-independent, non-cytotoxic, and combination differentiation treatments to salvage chemo-refractory mNPM1-AML.

VELOSANO 2 | ANNUAL REPORT 15Babal Kant Jha, Ph.D.PILOT AWARDDeveloping a Potent Pharmacologic Inhibitor of Sonic HedgehogTranscription Factor Glioma-Associated Protein (GLI) for theTreatment of Drug Resistant Myeloid LeukemiaPrincipal Investigator: Babal Kant Jha, Ph.D.Co-Investigator: James Phillips, Ph.D.Proliferation of hematopoietic stem and progenitors cells are tightly regulated and are quiescent understeady state condition however, they can be induced to proliferate by activation of various oncogenic signals.Recent studies suggest that signaling pathways involved in embryonic development including Hedgehog (Hh)signaling are aberrantly activated in leukemia. GLI genes, commonly known as Gli code, encode transcriptionfactors that regulate pro-survival genes at the distal end of the canonical Hh pathway. For the last severalyears the focus has been on targeting the Hh-GLI axis using inhibitors of SMO, an upstream modulatorof Hh-GLI signaling axis, which has met with limited success. This is because oncogene-driven signalingpathways, in particular RAS/RAF/AKT, circumvent the Hh-GLI axis to converge on and drive GLI to a higheractivating state. Thus, GLI serves as a node for the convergence of various oncogenic signals. Inhibition ofGLI-dependent transcription affords a unique mechanism of action. Using structure guided drug designingapproach we are developing a highly specific inhibitor of GLI that will terminate GLI induced transcriptiondetrimental for cancer cell survival. GLI proteins are constitutively activated in many types of human cancersthat include myeloid leukemia, epithelial cancers of the GI tract, brain tumors, melanoma, pediatric solidtumors, liver, lung, breast, pancreatic and prostate cancers. KRAS is mutated in 30% of all human cancers,and in ~40% of myeloid leukemia. Our current study directed towards the development of a new class of GLIinhibitors may have important impact for the treatment of various cancers.

Jaroslaw Maciejewski,M.D., Ph.D.VELOSANO 2 PILOT AWARDVIRTUAL RIDER Use of Metformin to Prevent and Treat Aging-Related Myeloid Neoplasia Principal Investigator: Jaroslaw Maciejewski, M.D., Ph.D. Co-Investigators: Daniel Lindner, M.D., Ph.D. and Tomas Radivoyevitch, Ph.D. Mutations are discrete defects in genes which if acquired in specific tissues can result in cancer. Many different mutations have been recently discovered which can either initiate or lead to progression of leukemia. Myelodysplastic syndrome is an example of a slowly progressing leukemia affecting increasing numbers of patients in the US. In MDS and many other leukemia’s one the most commonly altered (mutated genes) is called TET2. Mutations affecting the function of this gene promote leukemia and thus the defect in the gene may constitute a relevant target for specific drug development. To date, no targeted, selective drugs effective in TET2 mutations have been developed. Our hypothesis, supported by preliminary results, suggest that one could generate drugs that would increase the remaining activity of the partially damaged TET2 and therefore restore the appropriate function of this gene in leukemic cells. Our data also suggests that one of the already existing agents used in other disease may be effective in increasing TET2 function and overcoming the effect of mutations. If indeed mouse and other experiments to be performed in this project show that this is the case, we could quickly use an old drug in a new targeted application. Consequently, our proposed study has the potential to generate a new, effective and selective therapy for leukemia and MDS characterized by defects in the TET2 gene.

VELOSANO 2 | ANNUAL REPORT 17Edward V. Maytin, M.D., Ph.D.PILOT AWARDMinimally Toxic Approach for Breast Cancer Metastases:Capecitabine-Enhanced Photodynamic TherapyPrincipal Investigator: Edward V. Maytin, M.D., Ph.D.Co-Investigator: Sanjay Anand, Ph.D.Breast cancer (BrCA) that has metastasized to the skin of the chest wall is a particularly difficult problembecause these tumors are notoriously resistant to chemotherapy. Currently, the only effective option forlocal control of BrCA skin metastases is ionizing radiation therapy (RT); this shrinks the tumors afterrepeated treatments, but also causes severe side effects (blistering, chronic ulcers, and radiation dermatitis).Photodynamic therapy (PDT) is a new form of cancer treatment that in contrast to RT, causes no scarring,fibrosis, nor genetic mutations. PDT employs two components: (1) a drug, called a photosensitizer (PS),which builds up specifically within tumor cells; (2) intense visible light, which activates the PS to kill thecancer cells. PDT is currently used for treatment of superficial skin cancers such as basal cell carcinoma, andshould theoretically also work for cutaneous BrCA metastases. To increase the effectiveness of PDT for BrCA,we propose to combine PDT with a chemotherapeutic agent (capecitabine; CBN) already used routinelyfor breast cancer. Based upon our discovery that the active component of CBN has a remarkable ability toincrease PS accumulation within BrCA cells, we will ask whether giving CBN in combination with PS leadsto higher PS accumulation in tumors, as compared to the accumulation after giving PS alone. Experimentswill be performed in mice with cutaneous breast cancer. The results of this study, if positive, should allow usto propose a clinical trial of combination CBN-plus-PDT as a non-scarring alternative to RT for patients withcutaneous BrCA.

Alberto Montero, M.D.VELOSANO 2 PILOT AWARDVIRTUAL RIDER Targeting the Achilles’ Shield of Triple-Negative Breast Cancer by Androgen Blockade Principal Investigator: Alberto Montero, M.D. Co-Investigators: Jame Abraham, M.D. and Mohamed Abazeed, M.D., Ph.D. Breast cancer can be divided into four major subtypes: luminal A, luminal B, HER2 type, and triple negative breast cancers (TNBC). TNBC is the only breast cancer subtype that cannot be targeted with hormone therapy and/or trastuzumab (Herceptin). In part, this is why TNBC are more aggressive and have a poorer prognosis. Our research is focused on studying how specific gene changes in TNBC may be useful in developing new therapies. Namely, we have identified the receptor for the male hormone, androgen, as a key molecule for making some TNBC resistant to traditional chemo- and radio-therapy. Although several studies have shown that some women that contain the androgen receptor in their tumor may respond to drugs that block androgen signaling, our work suggests that a majority of women with TNBC that express androgen receptor can benefit from androgen blockade when combined with DNA damaging drugs or X-rays. Our proposal seeks to translate these findings to inform early phase clinical studies that will implement this new treatment paradigm in breast cancer.

VELOSANO 2 | ANNUAL REPORT 19Kwok Peng Ng, Ph.D. PILOT AWARD Non-Cytotoxic Probes to Renew AML Differentiation and Spare Normal Stem Cells Principal Investigator: Kwok Peng Ng, Ph.D. Co-Investigators: Yogen Saunthararajah, M.D. and Drew Adams, Ph.D. The human body is made up of specialized cells, e.g. liver cells, heart cells, etc. During gestation, these cells develop from a single fertilized egg cell to the billions of cells that form the complex multicellular body through a process known as cellular differentiation. Cellular differentiation persist in adulthood when adult stem cells produce daughter cells (progenitors) that rapidly divide and mature to the myriad of specialized cells required for tissue maintenance and repair. During each division, progenitors progressively specialize until they reach their terminal differentiated state where they stop dividing, e.g. becoming a heart cell or nerve cell. Cancer is a disease of unregulated progenitor growth emerging from gene mutations that blocks terminal differentiation. Conventional chemotherapy kills dividing cells indiscriminately by causing stress that activates a cell suicide program. Unfortunately, suicide program genes are the most commonly mutated genes in cancer cells, which in essence, removes the suicide program from these cells. Consequently, conventional treatments do not eradicate the cancer, but instead destroy normal dividing cells that have an intact suicide program, leading to the severe side-effects typical of chemotherapy. Our research will develop drugs for a new and distinctive approach to treating cancer that is based on restoring cancer cell differentiation rather than activating the cell suicide program. We have very promising molecules that we have identified through a search for compounds that renews cancer cell differentiation. We will improve these compounds with the goal of one day testing this non-toxic, non-suicide-based approach to treatment in the clinic.





Craig Peacock, Ph.D.PILOT AWARD VELOSANO 2 VIRTUAL RIDERMechanisms of Acquired Chemoresistence in Small Cell Lung CancerPrincipal Investigator: Craig Peacock, Ph.D.Co-Investigator: Mohamed Abazeed, M.D., Ph.D.With a world-wide, estimated 1.6 million new cases a year, cancer of the lung has easily been the mostlethal over the past several decades. While only 10-15% of these cases are diagnosed as small cell lungcancer (SCLC), it is nonetheless a major contributor to cancer deaths in its own right, due to the outsizedlethality of this disease. At first, most SCLC patients have disease that is very sensitive to chemotherapy, butthe almost inevitable emergence of a drug-resistant form of the cancer within 12 months of diagnosis, resultsin less than 5% of these surviving for five years. This dismal statistic has not changed for over thirty years.To deliver desperately needed, lasting treatment responses to these patients, we must find new approachesthat can be used to either prevent or delay the development of relapsed disease, or improve its clinicalmanagement. By establishing cutting-edge, laboratory models, we have both addressed the shortage of freshtissue that has hampered earlier progress in SCLC research, and enabled us to administer successive roundsof chemotherapy to tumors that are initially sensitive. We can then follow development of resistance in thesetumors, in real-time. This includes analysis of the genetic changes that accompany this process, with theexpectation of identifying a vulnerability via which we can significantly improve outcomes for these patients.

VELOSANO 2 | ANNUAL REPORT 23Jianfei Qian, Ph.D.PILOT AWARDDeveloping a DKK1-DC Vaccine for Immunotherapy of Multiple MyelomaPrincipal Investigator: Jianfei Qian, Ph.D.Multiple myeloma (MM) is a plasma cell cancer characterized by tumor cell accumulation in the bonemarrow; it remains incurable in most patients. Vaccination may help the immune system control diseaseearly and prevent MM progression. An effecive vaccine must include protein fragments that can recognizeMM cells and kill them. Currently we lack such a vaccine for MM because no one has found suitableMM-associated protein fragments. Our previous results show that a protein, Dickkopf-1 (DKK1), is highlyexpressed by MM cells from all patients studied and is absent in normal tissues except placenta and prostate.We also found certain immune cells called dendritic cells specifically recognized DKK1 and effectivelykilled MM cells in test tube experiments and mouse models of MM. We hypothesize that DDK1’s broadexpression in myeloma cells but highly restricted expression in normal tissues, together with its ability toinihbit the activity of bone-forming cells, make DKK1 an ideal and universal target for MM immunotherapy.To develop DKK1-dendritic cell vaccines for all MM patients, we identified a long DKK1 protein fragmentthat can potentially bind with immune system molecules crucial for immune recognition and killing of foreignmolecules and abnormal cells. In this project we will complete preclinical studies necessary for a first-in-human pilot study that we have designed. Completing this project will enable us to optimally translateour well-established myeloma vaccination concept into the clinic through collaboration between experts invaccines, MM immunology, and clinical care that is unique to our comprehensive cancer center.

Violette Recinos, M.D. PILOT AWARD Inhibition of Histone Methyltransferase with Novel Epipolythiodioxopiperazines (ETP) Alkaloids in Pediatric High Grade Glioma Principal Investigator: Violette Recinos, M.D. Pediatric high grade glioma (HGG), which ranks among the most deadly childhood cancers has recently been shown to be linked to certain genetic mutations. Two of these mutations within the histone H3.3 gene H3F3A (K27M and G34R/V) have been shown to be influenced by epigenetic factors whereby the cell’s environment can cause changes to the DNA and result in altered function. Our goal is to show that specific mechanisms related to these genes may be involved in tumor growth and contribute to therapeutic resistance and tumor recurrence. Targeting these pathways may provide a new therapeutic approach. We will expand preliminary results from our lab showing Chaetocin, a histone lysine methyltransferase (HMT) inhibitor, effectively killed 5 of 7 pediatric HGG including two with H3 K27M mutation to include four newly synthesized epipolythiodioxopiperazine (ETP) alkaloid derivatives. These ETP agents are structurally and functionally distinct and have been shown to be effective for cervical, lung, renal and breast cancer at low concentrations. We will evaluate ETP effectiveness on tumor growth and survival through in vitro and in vivo studies using tumor cells as well as non-tumor control cells. Results from this investigation will (1) advance our understanding of epigenetic regulation in solid brain tumors, (2) possibly show that epigenetic targeting may be more beneficial than or synergize with current therapies, (3) specifically identify agnets that may target the H3 K27M tumor subtypes and ultimately improve survival in pediatric brain tumor patients as well as other pediatric and adult cancers.

VELOSANO 2 | ANNUAL REPORT 25Brian Rini, M.D.PILOT AWARD VELOSANO 2 RIDERExploration of CD8+ T Cell Infiltration and Other Immune MicroenvironmentParameters in Primary Renal Cell Carcinoma Tumors as Biomarkers of Responseto Checkpoint Inhibitor TherapyPrincipal Investigator: Brian Rini, M.D.Co-Investigators: James Finke, Ph.D. and Christopher Przybycin, M.D.Harnessing the immune system to treat cancer has been a long sought-after goal in cancer medicine.Recently, a class of agents known as checkpoint inhibitors has been tested in patients with advanced cancersand has demonstrated anti-tumor effects. These agents effectively remove the brakes of a person’s immunesystem, allowing a patient’s natural anti-tumor immunity to kill cancer cells. We are now testing the safetyand effectiveness of these agents in patients with a type of kidney tumor called renal cell carcinoma. Patientswill be given one or two doses of either a single drug or a combination of drugs prior to surgical removalof the kidney tumor. The safety of this approach will be tested, along with whether or not these medicinescause the tumor to shrink. Importantly, many studies on the tumor tissue and blood will be done to look atspecific immune cell populations to see if they can predict which patients might benefit the most from thisapproach. The hope is that this clinical trial will lend insight to allow for the rationale further development ofthese agents in kidney cancer patients.

Steven Rosenfeld,M.D., Ph.D. PILOT AWARD Enhancing the Efficacy of Kif11 Inhibitors for the Treatment of Glioblastoma Principal Investigator: Steven Rosenfeld, M.D., Ph.D. Glioblastoma (GBM) is the most common and malignant of primary brain tumors. In spite of well over half a century of dedicated clinical research, the outcome for patients afflicted with GBM still remains grim. Three features particularly contribute to the highly malignant nature of this disease. First, GBMs, like many cancers, proliferate uncontrollably. Second, while these tumors rarely metastasize outside of the brain, they invade diffusely through the brain, producing a profound degree of neurological disability. Finally, GBMs, like several other cancers, contain within them a small population of cells—referred to as “tumor initiating cells” (TICs)—that are highly resistant to conventional treatment and which cause the inevitable recurrence of tumor after radiation and chemotherapy. What is desperately needed is a “target” that is required for both GBM proliferation and invasion, and for survival of both TICs and nonTICs alike. The underlying theme of this proposal is that the mitotic kinesin Kif11 is an ideal target for GBM. We have recently shown that clinically available Kif11 inhibitors kill both TICs and nonTICs and also block GBM invasion. However, translating these encouraging laboratory results into a treatment that benefits patients in the clinic will require that we address two questions: 1) how can we prevent the development of resistance to Kif11 inhibitors and 2) how can we optimize the delivery of these inhibitors to brain tumors. Our central hypothesis is that targeting resistance to Kif11 inhibitors and enhancing their delivery/retention in the CNS can make them very effective GBM therapeutics with minimal local toxicity and reduced systemic toxicity.

VELOSANO 2 | ANNUAL REPORT 27George Stark, Ph.D. PILOT AWARD New Strategies for the Preferential Killing of Cancer Stem Cells Principal Investigator: George Stark, Ph.D. Co-Investigator: Sarmishtha De Most tumors consist of two types of cells. The major type is sensitive to many drugs, and the killing of these cells is responsible for the initial favorable responses that are often observed. Unfortunately, tumors also contain a minor type, called cancer stem cells, and the regrowth of an initially sensitive tumor is likely to be due to the ability of these stem cells to resist most therapies. We are seeking novel points of vulnerability of cancer stem cells, so that therapies can kill both tumor cell types initially, thus avoiding recurrence. We have found that a new drug, CBL137, kills both stem and non-stem cancer cells, but remarkably kills the stem cells preferentially. The drug works by preventing the expression of proteins that are essential for cancer stem cell survival. Current Phase I clinical trials show that CBL137 has minimal toxicity at effective doses. In initial experiments with a mouse model of glioblastoma, we show that administration of CBL137 in the drinking water provides a substantial improvement in survival from human tumors that have been implanted into the brains of the mice. We are also working with a second class of drugs, called STAT3 inhibitors, which are also reported to kill cancers stem cells preferentially. We will now test the beneficial effects of CBL137 and STAT3 inhibitors alone, in combination with each other, and in combination with standard-of- care therapies, using stem cells from cancers of the breast, prostate, and lung. Positive results can quickly be translated to clinical trials.

Angela Ting, Ph.D.PILOT AWARDUnderstanding the Full Spectrum of Epigenetic Vulnerability in Cancer Throughthe Delineation of DNA Methylation Function in Gene 3’ EndPrincipal Investigator: Angela Ting, Ph.D.Abnormal DNA methylation (an epigenetic mark) is a hallmark of human cancers, and drugs that target theDNA methylation machineries are used for treating certain cancers. However, effective targeting of DNAmethylation changes as a cancer therapy demands a full understanding of the biological impact of thesecancer-associated defects so that we can exploit all aspects of epigenetic vulnerability in cancer as well asanticipate unintended side effects of any epigenetic therapy. DNA methylation in the beginnings of genes(promoters) can shut off gene expression without affecting the DNA sequence, much like a light switchturning off a lamp without cutting the wires. Through whole genome mapping efforts, we now appreciatethat cancer-associated DNA methylation frequently occur in the ends of genes (3’ ends). In colon cancer, wediscovered a novel association between DNA methylation at gene 3’ ends and RNA processing, which canresult in the production of different amounts of the protein or altered proteins with unique functions. Ourobservation raises the exciting possibility that DNA methylation can affect gene expression not only as an on/off switch in gene promoters but also analogously to a dimmer switch modulating light levels when it occursin gene 3’ ends. We aim to delineate how gene 3’ DNA methylation regulate RNA processing and anticipatesuch knowledge to broadly and significantly aid in understanding of how cancer behaviors are shaped bynon-promoter DNA methylation. Ultimately, these insights will accelerate our ability to develop therapiestargeting epigenetic changes in cancer.

VELOSANO 2 | ANNUAL REPORT 29Bin Zhang, Ph.D.PILOT AWARDNovel Roles of LMAN1 Mutations in Colorectal Cancer DevelopmentPrincipal Investigator: Bin Zhang, Ph.D.Every year over 50,000 people die of colorectal cancer, making it the third most common cause of cancerdeath in the United States. Genomic studies have shown that colorectal cancer is a highly heterogeneousdisorder. Subgroups of cancer, defined by different combinations of gene mutations, may not respond wellto the standard course of treatment and require more personalized therapies. Finding and understandingnew pathways associated with oncogenes and tumor suppressor genes are critical for developing the mosteffective personalized treatment approaches. We have shown that a gene (LMAN1) previously not knownto be associated with cancer is frequently mutated in colorectal cancer. Patients lacking LMAN1 expressionhad significantly worse prognosis than those with normal LMAN1 expression. LMAN1 is involved incontrolling protein secretion. Our in vivo and in vitro studies support a hypothesis that LMAN1 functions asa novel tumor suppressor by regulating the secretion of interferon beta. This proposal is aimed at identifyingmolecular mechanisms for the loss of LMAN1 expression in colorectal cancer and understanding how LMAN1mutation promotes formation and development of colorectal cancer. Although interferon is effective againstcertain types of leukemia and melanoma, it has not been indicated for colorectal cancer treatment. Ourresults suggest that a subgroup of patients with LMAN1-deficient cancer can also benefit from an adjuvantinterferon beta therapy.

Case Comprehensive CancerCenter Pilot AwardsCleveland Clinic is part of the CaseComprehensive Cancer Center (CCC), whichis designed to promote research collaborationacross the three member institutions:Cleveland Clinic, Case Western ReserveUniversity, and University Hospitals. Teamscience is increasingly important for successfulcancer research, and the Case CCC is anexcellent example of such teamwork, workingacross these three organizations.Case CCC had numerous teams participate inVeloSano 2, and as part of our collaborationthey received $250,000 of the VeloSano 2total raised. They used these funds to grantfive Case CCC VeloSano Pilot Awards that aredetailed on the following two pages.

VELOSANO 2 | ANNUAL REPORT 31PILOT AWARDTargeting the cAMP-CREB1 Axis to Treat PlatinumResistant High-Grad Serous Ovarian CancersPrincipal Investigator: Analisa DiFeo, Ph.D.Co-Investigator: Vinay VaradanThis project is a collaboration between PI Analisa DiFeo, a basic/translationalcancer researcher focusing on ovarian cancer, and Co-PI Vinay Varadan, acomputational cancer genomics researcher. They aim to identify novel pathwaysfor the targeted treatment of chemo-resistant ovarian cancer. The proposalinvolved the application of a computational method, termed InFlo, to identifydysregulated groups of genes from mRNA expression data. They present solidpreliminary data showing that cAMP activity mediates platinum resistance inovarian cancer, and they propose that a specific CREB1 inhibitor H-89 can beused in combination with platinum treatment to overcome resistance to thelatter. Two aims are proposed: Aim 1: Assess efficacy of H-89 on overcomingplatinum resistance in vivo. Aim 2: Identify pharmacodynamics and therapeuticsusceptibility biomarkers of H-89 and platinum therapy in PDX models.PILOT AWARDDevelopment of Intravenously Injectable ß-GlucanTreatment for Regulating Granulocytic Myeloid-DerivedSuppressive CellsPrincipal Investigator: Julian Kim, M.D.Co-Investigator: Mei ZhangThe proposal is based on preliminary data developed by Dr. Zhang demonstratingthat ß-glucan structures (particularly BG34) can alter the suppressive immunityfunction of granulocytic MDSC (Gr-DMSC) towards and inflammatory (M1)phenotype, and the observation made by Drs. Kim and Zhang in their ongoingpolyclonal T-cell immunotherapy trial in melanoma of the emergence of anincrease MDSC population following adoptive T-cell transfer.This is a proposal based upon exploring the impact of a soluble beta-glucan, BG34, or Gr-MDSC’s that are through to be important in cancer. Theinvestigators believe that the administration of this agent has potential as animmunomodulatory strategy for cancer therapy. The proposal seeks to study theeffects of BG34 on GR-MDSC’s in vitro using mouse and human cells and usinga mouse melanoma model system.

PILOT AWARDIdentification of Surface Proteins Requiredfor Internalization of Therapeutic ExosomesPrincipal Investigator: Huiping Liu, M.D., Ph.D.Co-Investigators: Cliff Harding, Jan Olof LÖtvall and Cheryl ThompsonThis proposal looks to identify differences in exosome surface proteins and interrogate how thisimpacts the dynamics of cellular uptake. As multiple cell types generate exosomes, generating thisinformation is critical for future mechanistic studies and therapeutic development.PILOT AWARDDevelopment of New Type of Therapeutics Selectively Targeting Bax or BakPrincipal Investigator: Shigemi Matsuyama, DVM, Ph.D.Co-Investigator: Drew AdamsThis is a proposal based upon identifying novel small molecules that regulate BAX/BAK-mediatedcell killing. The investigators have developed a cell based tet-inducible model system that has beenvalidated and tested using some compound libraries. This work has led to the identification of severalhits that will be explored further along with new hits from their proposed screening.PILOT AWARDDevelop HTS Assay for Screening GPT2 Inhibitorsto Target P13KCA-Mutated Colorectal CancersPrincipal Investigator: Zhenghe (John) Wang, Ph.D.Co-Investigator: Drew AdamsThe preliminary evidence underlying this proposal is strong, suggesting that GPT2-specific inhibitorswill be more potent and less toxic than Aminooxyacetate (AOA), an inhibitor of GPT2 which is non-specific as it inhibits and transaminases, and thus would have a more favorable therapeutic indexthan AOA. PIK3CA, which encodes the p110a catalytic subunit of P13K, is the most frequentlymutated oncogene in human cancer.

VELOSANO 2 | ANNUAL REPORT 331 IMPACT AWARD Precision Targeting of Therapeutic Resistance in Cancer Principal Investigators: Mohamed Abazeed, M.D. (1), Ph.D. and Shlomo A. Koyfman, M.D. (2) Abazeed VELOSANO 2 RIDER | Koyfman VELOSANO 2 VIRTUAL RIDER Patients that do not respond to traditional cancer therapies have the poorest clinical outcomes and suffer due to resistance of their tumor to palliation. Our research program focuses on identifying the genetic changes that give rise to resistance in cancer and to use this information to develop personalized treatment strategies. We have generated a large body of data describing the genetic landscape of resistance in cancer and we are focused on targeting specific genetic changes with greater precision. To advance the translation of these findings, we have coupled the Cleveland Clinic’s robust clinical infrastructure with state-of-the-art methodology developed in our laboratory to develop primary xenografts from several cancer lineages. These avatars of human cancers are ideal platforms for enhancing the genetic understanding of cancer because they recapitulate the genetic complexity of human tumors. Our team is poised to lead the incorporation of these2 models into clinical practice. IMPACT AWARD Preserving the Fertility of Women with Cancer: Ovarian Tissue Freezing Principal Investigators: Tommaso Falcone, M.D. (3), Rebecca Flyckt, M.D. (4) As treatments for cancer become increasingly effective, more women are surviving their cancers and focusing on childbearing. Unfortunately, the treatments involved in effective cancer care can also be severely damaging to the ovaries. Many women suffer menstrual dysfunction, infertility, or premature menopause after their cancer treatments. Until recently, women undergoing chemotherapy had limited options for fertility preservation. The gold standards, egg and embryo freezing, cannot be used for girls who have not undergone puberty, and they are3 also not options for adult women who must pursue immediate treatment of their cancers. In the past several decades, ovarian tissue freezing has emerged as a promising new approach to fertility preservation in adult women and girls. Instead of a handful of eggs or embryos, frozen ovarian tissue may contain thousands of viable oocytes. To date, at least 60 live births have been recorded worldwide using this technique, and the numbers are increasing every year. The American Society of Reproductive Medicine still considers ovarian tissue cryopreservation to be experimental in humans and this procedure can only be performed under an IRB approved protocol with detailed informed consent. Cleveland Clinic now offers ovarian tissue freezing for both pediatric and adult populations under such a protocol. The protocol involves a brief minimally invasive surgical procedure to harvest the tissue and then the tissue can frozen and reimplanted years later once treatments are complete and fertility is desired. Ovarian tissue freezing provides an opportunity for fertility preservation to patients who might not otherwise have any options. We are excited to be offering this innovative treatment at Cleveland Clinic for those who need it.4

IMPACT AWARD 1 2Colon Cancer Metastasis 3 4Principal Investigators: Emina Huang, M.D. (1) and Xiaoxia Li, Ph.D. (2) 5The purpose is to define the underlying clinical and molecular behavior of this most lethal presentation of colon cancer,to identify new strategies to prevent progression from localized disease to metastatic disease, and to save lives fromthis disease.Increasingly, patients present with metastatic colon cancer that require combined management by surgeons andmedical oncologists, both of whom are advised by pathologists. This project brings together insights from these threedisciplines as well as the molecular expertise from the Lerner Research Institute to tackle both the understandingand treatment of metastatic colon cancer. Survival is dismal. Even in best case scenarios more than 50% of patientswith metastatic disease die from cancer. A better understanding of this disease leading to novel treatment approachesis clearly needed. First, we will examine the microenvironment of both primary and metastatic cancer lesions withexamination of stromal elements including lymphocytes and fibroblasts. Another element of this microenvironment,required for all tumors to grow and to metastasize, is the vascular supply. Secondly, we will examine these lesionswith regard to epigenetic regulation, well known to exert regulation in both primary and metastatic lesions.IMPACT AWARDCancer ThrombosisPrincipal Investigators: Alok Khorana, M.D. (3) and Keith McCrae, M.D. (4) Khorana & McCrae VELOSANO 2 RIDERSThis project will consist of new clinical research programs that explore novel approaches to the management andprevention of cancer-associated thrombosis. These programs focus on clinical trials that employ agents such asstatins, anti-platelet agents and direct oral anticoagulants. These trials, as well as a newly-opened cancer thrombosisclinic (CAT) are a rich source of clinical samples for analyses that will be performed. New biorepositories containingsamples from patients with glioblastoma, pancreatic cancer and leukemia have been developed over the last year, anda forth biorepository focusing on patients presenting to the CAT clinic for evaluation of venous or arterial thrombosiswill be initiated. The goals of our studies will be to (1) better define basic mechanisms that underlie the developmentof venous and arterial thrombi in patients with cancer, in particular those receiving chemotherapy, (2) test the efficacyof novel anticoagulants and anti-platelet agents in cancer by developing quantifiable measures of platelet, hemostaticand vascular activation in patients that will be assessed before and during therapeutic interventions, (3) developanimal models of cancer-associated thrombosis to allow development of mechanism-based interventions, and (4)create and expand biorepositories of fractionated plasma, leukocytes, platelets and microvesicles that will be aninvaluable resource for future initiatives.IMPACT AWARDChronic Myelomonocytic Leukemia (CMML)Principal Investigator: Jaroslaw Maciejewski, M.D., Ph.D (5) Maciejewski VELOSANO 2 VIRTUAL RIDERChronic Myelomonocytic Leukemia (CMML) is a protracted and progressive leukemia occurring mostly in the elderly.With the increased life expectancy of the US population, the number of individuals affected by this condition isexpanding, lending increasing urgency to the proposed investigations. CMML represents a continuum of clinical stages,including low-risk disease, advanced CMML and CMML-derived secondary acute leukemias (sAML). In addition, manyearly, indolent cases remain unrecognized, labeled as reactive monocytosis of unclear significance. Our investigatorswill also involve these entities.The overarching aim of our proposal is the creation of a center for treatment of CMML, that, due to clinical andresearch excellence, will achieve national and international recognition. The short-term goals of the center will includeimproved management of CMML. Long-term goals will include development and application of curative therapies forCMML. The scientific focus is on the introduction of effective targeted therapies to be developed through a team effortof laboratory scientists, medicinal chemists and clinicians. Members of our team have already established a trackrecord of scientific productivity and fruitful collaborations that have contributed to progress in CMML.

Partners Make VeloSano Possible VELOSANO 2 | ANNUAL REPORT 35The financial and/or in-kind support of our partners allows FOUNDINGVeloSano to successfully and safely operate the event, aswell as allocate every dollar raised by participants directly CONTRIBUTINGto cancer research at Cleveland Clinic. Thank you to eachand every one of our amazing partners – we couldn’t do thiswithout you! SUPPORTINGSPOKE PEDAL AXLEMEDIA SPECIAL THANKS BIKE SHOP star HARLEY-DAVIDSON TM

Big Wheelers presented by KeyBank Steve Penton Tim Spiro Tracy Pesho Nick StambulaOur Big Wheelers are Riders who at least double their minimum fundraising Matt Peters Randall Starlingcommitment, thereby accelerating the pace at which we can impact advances Nicole Peters Andy Stephensonin cancer research. There were 228 Big Wheelers in VeloSano 2, and each one Michael Petras Tim Stoverearned a cozy VeloSano Big Wheeler fleece to wear proudly around town. Help us Michael A. Petras Rich Stovskysend a Big Thank You to our Big Wheelers – they’re a big deal! Katherine Petrey John Suh Brad Pohlman Bart SwainPete Accorti Paul Cusato Lauren Hanna Anna Lowenstein Julia Pollock SheilaRoss Agnor Curtis Danburg Marc Harrison Christine Lynch Larry Pollock SwartzlanderVlad Agranovich Tyler Danburg Kathy Hart Kevin Lynn Jason Radel Jeff SysloBenito Alvarez Jonathan Dandes Larry Hatch Nancy Lyon-Stadler Sunay Rastogi Ilaria TamagnoMichelle Amato Jerry Davidson Dan Haynes Paul Madonia Craig Reagor Kelly TompkinsJohn Anderson Jillian Davis Graham Hearns Alane Malerick Sharon Reichart Mike TothKeith Arian Lynn Dieter Matt Hein Kate Malone Feza Remzi Mary TothSandra Avis Paul Dolan Brian Held Craig Manchen Bob Rich Colleen TredwayGreg Avis Kevin Dooley Mike Hermsen Lisa Manning Paul Rich Shane TurnerKathy Bass Dave Doren Angela Higham Matt Manosky Brian Rini Robbie TwellsMike Bauer John Dougherty Larry Hirsh Scott Marlow Bill Riter Rodney TwellsColeen Don Dreier Richard Hollington Deborah Marotta Tom Roe Barry UnderwoodBecker-Dowdall Alan Duffy Michael Jacobs Robert May Mark Rood Jason ValentCraig Belec Stephanie Duffy Vickie Johnson Keith McCrae Mark Ross Jack VarneyLaurie Benic Jack Efta Steve Jones Robert Mccreary Tom Roulston Rose VinyMike Bosner Courtney Eiler Andy Jones Linda McHugh John Saada Dominic VisconsiNancy Bradshaw Bassam Estfan Deborah Junior Jamie McKeon Cindy Sackett Bob WaitkusMark Brandt Doug Fanta Steve Karklin Daniel McNeil Jessica Sacks Sally WajahnAli Brawner David Faturos Matt Keppler Tom Milewski Joe Santoli Rob WatsonSarah Tim Fenner Jeff King Laura Mimura Joe Scaminace Robin WeaverBrawner-Dyke Judy Ann Forbes Larry Klein Robbie Mocilnikar Bill Schiemann Ron WeinbergSteve Briggs Amanda Fox Stewart Kohl Jessica Mocilnikar William Schiemann Terri WeinbergChad Broski Hiroyuki Fujita Donna Kohl Greg Montagano Ryan Schreiber Morris WheelerMarc Byrnes John Fung Zach Komorski Dan Moore Morgan Schreiber Shirley WhiteJulie Callsen Beth Fung Cindy Koury Edward Moore Brittany Schreiber Jeff WilsonDenise Carkhuff Monica George Kreiner Jeff Moore Matt Segal Kelly WolffJeff Carpenter Gali-Chardiet Lisa Krejci Mike Mullen David Seiger Blair WoodHetty Carraway Fred Geis Amy Kubacki Bill Mulligan Renee Singley Donald WrobleBob Case Fran George Jeff Kula Latham Murfey John Sinnenberg Kirk ZehnderAJ Chardiet Stan Gerson Anthony LaPlaca Brad Nagle James SoukupArmando Chardiet Samir Ghousheh Margaret LaPlaca Jen NeundorferVictoria Chardiet Dave Grinnell Samantha LaPlaca Michael OhmThomas Chung Ira Grossman Justin Lathia Dario OrtizTom Cicarella Beth Grubb Amanda Lathia Len PagonAndy Clarke Lindsay Guzowski Eric Laurence Alan PapaMichael Coburn John Haas Dennis Lehman Armida ParalaJoanne Cohen Darin Haines Alicia Lenhart John PatrickTerence Connor Steve Hallam Brinton Lincoln Rob PawlakChandler Converse Cassi Handler Matt Litzler Brad Peck

VELOSANO 2 | ANNUAL REPORT 37VeloSano 2 Steering Committee Pete Accorti Talan Products Phil Alexander BrandmuscleC O - C H A I R S (Below, L-R) Mike Bauer Master Lock Company LLC Mark Brandt McGladreyStewart A. Kohl The Riverside Company Bill Braun EatonPaul J. Dolan Cleveland Indians Marc Byrnes Oswald Companies Kara Carter Orion Advisory, LLCMEDICAL CHAIR Armando Chardiet Cleveland ClinicBrian J. Bolwell, M.D. Loren Chylla The Adcom Group, Inc. Andy Clarke Blount InternationalHONORARY CO-CHAIRS Joanne Cohen Cleveland Clinic Chandler Converse CBRE | Brokerage ServicesJohn Anderson WKYC Channel 3 Delos Cosgrove, M.D. Cleveland ClinicNorma Lerner The Lerner Foundation Sam Covelli Covelli Enterprises Caroline El Sanadi Case Western Reserve Univ.T E A M V E LO S A N O (Below, L-R) Trina Evans KeyBank / KeyCorp Samir Ghousheh Cardinal HealthMohammed Farunia, Associate David Gilbert Greater Cleveland Sports CommissionKandis Schreiber, Director Marcus Glover Horseshoe Casino ClevelandNicole Peters, Senior Director David Goodman Squire Patton Boggs Beth Brand, Assistant Director Jerry Grisko CBIZ, Inc. Jack Haas Sensical Companies / UN1TUS Brian Hall Innogistics LLC Marc Harrison, M.D. Cleveland Clinic Jody Herzog Fleet Feet Sports Tom Hileman Hileman Group Andy Jones MCPc Steve Jones, M.D. Cleveland Clinic Craig Manchen Retired Former Owner (Highland Group Industries) Paul Matsen Cleveland Clinic Linda McHugh Cleveland Clinic Heather Moore Heather Moore Jewelry Bill Mulligan Primus Capital Jennifer Neundorfer flashstarts Len Pagon Next Sparc, LLC Mike Petras Cardinal at Home / Cardinal Canada Larry Pollock Lucky Stars Partners LLC Lauren Rich Fine Howard & O’Brien Inc. Tim Richards Cleveland New 102-FM Joe Roman Greater Cleveland Partnership John Saada Jones Day Mark Siegel Forest City Enterprises Renee L. Singley The Lerner Foundation John Sinnenberg Cyprium Capital LT Slater Takoda Group LLC Jacob VanSickle Bike Cleveland Morris Wheeler Drummond Road Capital Inc.

The Future of CancerCare at Cleveland ClinicPatient Support Is Paramount in New Cancer Facility Light and Space for PatientsThe psychological impact of a cancer diagnosis is profound. “When someone The open-plan first level — suffused with natural hears that they have cancer, it is a life-changing two or three seconds,” says light from floor-to-ceiling windows — also will Cleveland Clinic Taussig Cancer Institute Chairman Brian J. Bolwell, M.D., FACP. contain an outpatient pharmacy; a retail store“They are filled immediately with anxiety and fear. A cancer diagnosis may not stocked with items to meet cancer patients’ needs, always be a medical emergency, but it is always a psychological emergency.” such as skin care lotion for dry hands; and a Cleveland Clinic’s new cancer care building, opening in 2017, is designed cafeteria with food offerings to accommodate for easy access to the array of patient support services intended to reduce special dietary needs and medical conditions. cancer’s psychological stress. Those services will occupy most of the first floor of the $276 million, 377,000-square-foot outpatient tower currently under The first floor will be home to: construction. • A resource center where patients and familiesConserving Resources, Aiding Well-Being can access printed and online cancer information.“We strongly believe in the benefits of such programs, which range from reiki to relaxation therapy to mentoring,” Dr. Bolwell says. “They are not always easy to • Art and music therapy spaces. quantify scientifically. But what we do know is that patients with cancer and a • A boutique where patients with chemotherapy psychiatric diagnosis consume six times more healthcare resources than those without a psychiatric diagnosis. If you manage anxiety and other stress-related associated hair loss can receive free wigs, caps issues, you can significantly reduce resource utilization. It is also the right thing and scarves. to do for the well-being of patients and their families.” Dr. Bolwell and other Cleveland Clinic officials toured numerous cancer facilities around the country to • A wellness center for reiki, reflexology, guided compile best-practice ideas for the new building’s design. Patient comfort and convenience were paramount on their lists. “In almost every cancer facility, the imagery, facials and other aesthetic services. thing that I really did not like were the lines in which patients had to wait to get their blood drawn,” Dr. Bolwell says. “A quote from a cancer patient that sticks • A private prosthetics fitting area. with me is, ‘If I have six months to live, waiting four hours to get chemotherapy • The 4th Angel Mentoring Program, an initiative is a big deal to me.’ We have dedicated a lot of space in the new building to try to make sure that does not happen.” That includes a sizable blood-testing begun by figure skating champion and Cleveland laboratory on the first floor. Clinic cancer patient Scott Hamilton to provide patients with free, confidential, one-on-one advice and support from a trained volunteer and cancer survivor. • A spiritual area where patients and families can go for prayer or meditation. “There is a reason for having all these services on the first floor of our new cancer center,” Dr. Bolwell says. “We want to show patients as they first walk in that this is a warm and inviting atmosphere, and that we understand what they are going through. We understand that they are scared, and we have a lot of caregivers and programs right in front of them to help.”

The Power of Every One Centennial Campaignfinished 2015 with $175.8 million in totalcommitments for the year, bringing the overalltotal to more than $860 million. Launchedin 2014, the historic $2 billion philanthropiccampaign will continue until Cleveland Clinic’s100th anniversary in 2021. Every gift thatsupports the campaign is helping to make thehighest-quality healthcare accessible to thegreatest number of people through projectsand programs that put patients first, includingthe new Cleveland Clinic Cancer Center toopen in 2017.

9500 Euclid Avenue DVB WEB FACEBOOK Cleveland, Ohio 44195 velosano.org VeloSano 216.444.6150 | [email protected] TWITTER INSTAGRAMVELOSANO 4 | SAVE THE DATE @bikeVeloSano @bikeVeloSano July 21–23, 2017