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Golfers Against Cancer
2017 Summary

The 2017 Golfers Against Cancer Tournament and Gala were major successes and we were able to provide $145,000 to the University of Colorado Cancer Center for 3 research projects. All three projects involve collaboration of experienced scientists working together to test novel ideas in cancer research where innovation is a key criterion required to achieve funding through agencies such as the National Institutes of Health (NIH). Based on the success of the researchers that we have supported in the past, we expect that these pilot funds will be leveraged into larger research grants from the NIH and other agencies. In this way, our efforts are a catalyst for research, analogous to venture capital funding for entrepreneurs.

In 2017, we funded six outstanding researchers through two projects focused on basic mechanisms of cancer and one project on head and neck cancer:

Dr. Jay Hesselberth, PhD, is an Associate Professor in the Department of Biochemistry and Molecular Genetics at the University of Colorado Anschutz Medical Campus. He has teamed with Dr. James DeGregori, PhD, a Professor in the same department, on a project entitled “Multiplexed detection of DNA repair capacity for cancer diagnostics”. The goal of their project is to develop a novel sequencing-based assay for measuring DNA repair capacity that can be scaled to measure repair events catalyzed by endogenous activities in cells, both normal and cancerous. If successful, the assay may serve as a means to acquire specific information from cancer cells that supports precision medicine-based treatments in the future.

A team of investigators comprised of Joaquin Espinosa, PhD, a professor in the Department of Pharmacology at the University of Colorado Anschutz Medical Campus, Matthew Galbraith, PhD, an Instructor in the Department of Pharmacology, Natalie Serkova, PhD, a Professor in Anesthesiology, Radiology, Radiation Oncology and Pharmacology, and William Old, PhD, an Assistant Professor of Molecular, Cellular and Developmental Biology at the University of Colorado Boulder. The objectives of the project entitled “Identifying CDK8-based combinatorial therapeutic strategies” are to identify novel CDK8-based combinatorial therapeutic strategies, and to initiate preclinical studies to test their effectiveness with the ultimate goal is to generate the preclinical data required to bring CDK8-based therapies closer to the clinic.

Sana Karam, MD, PhD, an Assistant Professor in the Department of Radiation Oncology, University of Colorado Anschutz Medical Campus will collaborate with Antonio Jimeno, MD, PhD, Department of Medical Oncology to complete a project entitled “Radiotherapy for sensitizing poorly immunogenic tumors to immunotherapy”. The goal of the studies is to develop rational combination therapies in which radiotherapy and novel immunotherapies are delivered in precise ways to greatly enhance the efficacy of either strategy alone in head and neck cancers. The long-term goal is to use the findings to positively influence clinical trial design and head and neck cancer patient treatment.

In past years, the Denver Chapter of Golfers Against Cancer has funded research on blood cancers (leukemia), gastrointestinal cancer (colon, pancreas, etc), bladder cancer, breast cancer, liver cancer, lung cancer, head and neck cancer, as well as childhood cancers and general mechanisms of cancer development and prevention.

To make a direct donation to support cancer research through the Golfers Against Cancer, Donate Now. If you are interested in supporting a particular area of cancer research (e.g. breast cancer, childhood cancer, etc), with an individual donation of $25K or more (Donate Now), you can help solicit applications in that area and help select from among the applications.

Why Pilot Funding is so important for Cancer Research

The National Cancer Institute (NCI) is the largest funder of cancer research in the world and has an annual budget of about $5 billion. While this seems like a lot, less than 10% of research proposals sent to the NCI are funded. A successful application must contain extensive “preliminary data” to be favorably reviewed and eventually awarded. This creates a “Catch 22” of sorts: a researcher must spend money to generate preliminary data in order to compete successfully for money from the NCI to complete the project. The result is that many great ideas cannot be explored due to a lack of funding.

This is where you and Golfers Against Cancer make a difference. Golfers Against Cancer donates 100% of its proceeds for cancer research projects in the earliest stages. Through pilot grants of about $50,000 to research groups, Golfers Against Cancer funds great ideas that might never be explored without our support. This allows the researchers to generate the preliminary data that they need to compete for larger NCI grants.

Since 2009, Golfers Against Cancer has funded 21 great ideas. Many of these pilot projects have led to larger grants from the NCI, and more importantly, significant discoveries in cancer biology and therapy. For example, one $50,000 pilot grant to a molecular biologist, a computational biologist and a pediatric oncologist led to 2 grants from the NCI totaling over $2 million toward leukemia and lung cancer research, and a clinical trial that is in development.

To help Golfers Against Cancer fund more cancer research pilot projects, please Donate Now.

Leukemia Research

Leukemia is a cancer of the blood system. It is the most common cancer in children and can be very challenging to treat in children and adults. Golfers Against Cancer has funded 2 teams of leukemia researchers since 2009.

In 2010, Drs. James DeGregori, Aik-Choon Tan and Christopher Porter proposed to create a computational algorithm for the analysis of large-scale experiments exploring the function of most human genes in specific contexts. This algorithm and experimental approach have been used to identify vulnerabilities in leukemia cells as well as several other cancer types. The work in leukemia identified an unexpected protein that can be inhibited with a new drug, and the researchers are working to develop a clinical trial adding this drug to conventional chemotherapy for leukemia.

In 2012, Dr. DeGregori teamed up with Dr. Brian Reid to study how leukemia develops, particularly after exposure to ionizing irradiation. They found that blood cells activate a particular protein after radiation exposure that impairs the cells’ fitness, and creates a context that makes cancer development more likely. They are now studying the impaired cell fitness in more detail, with the hope that they may be able to improve cell fitness and reduce the likelihood of leukemia after radiation exposure.

Gastrointestinal Cancer

Gastrointestinal (GI) cancers include colorectal, gastric and pancreatic cancers. Colorectal cancer is the third most common cancer found in men and women in the United States (not counting skin cancers). Overall, the lifetime risk of developing colorectal cancer is about 1 in 20. Pancreatic cancer is more rare, but carries a

2016 DGAC Check to UCCC2016 Check Presentation to UCCC

guarded prognosis, as it is often in advanced stages when it is diagnosed.

In 2009, Golfers Against Cancer funded a project directed by Drs. Wells Messersmith and Colin Weekes, in which they sought to develop a gastrointestinal (GI) cancer tumor bank, focused on colorectal and pancreas cancer. This tumor bank is linked with detailed information about each tumor in the database. Using the samples and the data researchers can investigate ideas such as factors that lead to tumor response to treatment and patient prognosis.

Breast Cancer

Breast cancer is the most commonly diagnosed cancer in women and is the second leading cause of cancer death among women. Yearly, over 252,710 women in the US are diagnosed with breast cancer and more than 40,500 will die.

In 2016, the GAC supported a project directed by Drs. Traci Lyons, PhD and Kirk Hansen, PhD to explore the role of Sem7a in breast cancer progression with the goal of identifying how Sem7a may alter the normal cells that reside within breast tumors and lead to cancer metastasis. The project generated preliminary data that led to successful funding of an NIH R01 ($1,143,750 direct for 5 years) entitled “Deciphering COX2/SEMA7A dependent mechanisms of breast tumor progression” and an American Cancer Society Grant ($495,000 direct for 3 years) entitled “Investigating the role(s) of SEMA7A in breast tumor progression”.

Also in 2016, the GAC support Drs. Jill Slansky and Virginia Borges on a project to identify the T cell receptors shared among survivors to set the stage for generating a triple negative breast cancer vaccine to activate the memory T cells to eliminate any breast cancer cells that may result in recurrence.

Bladder Cancer

Bladder cancer usually affects older individuals. There are about 75,000 new cases of bladder cancer per year in the United States. Chemotherapy is effective for only some patients, but doctors cannot predict which patients will benefit.

In 2014, Drs. Dan Theodorescu and James Costello teamed up to combine experimental approaches and computational analyses to determine what genes are involved in bladder cancer cells’ response to chemotherapy. With this knowledge they hope to be able to predict which patients are most likely to benefit from chemotherapy.

Liver Cancer

Liver cancer affects about 35,000 people per year in the United States, usually older adults. Liver injury is one of the most common risk factors for liver cancer, including from heavy alcohol use and from hepatitis viruses.

In 2011, Golfers Against Cancer funded a project led by Drs. Barton, Hesselberth and Rosen to develop new methods to study how Hepatitis C virus avoids the immune system and persists in the liver, causing chronic damage and raising the risk of cancer. These methods are also being used to study other viral processes, amplifying the impact of this project.

Lung Cancer

Lung cancer, the leading cause of cancer death among men and women accounts for about 1 out of 4 cancer deaths. Each year, more people die of lung cancer than of colon, breast, and prostate cancers combined.

In 2016, Golfers Against Cancer funded a project led by Drs. Clambey and Nemenoff to define markers that predict which lung cancer patients benefit from immunotherapy and to develop a better understanding of the mechanisms underlying resistance to immunotherapy. Since initial funding in 2016, the project has supported three publications and grant proposals to the NIH and the Department of Defense.

Head and Neck Cancer

Head and Neck Cancer is usually a squamous cell carcinoma in the nasal cavity, paranasal sinuses, mouth, salivary gland, or throat. Risk factors include chewing or smoking tobacco and excessive alcohol use, and 25% are associated with human papilloma virus.

In 2014, Golfers Against Cancer funded Drs. Pyeon, Greer and Song to study how Human Papilloma Virus causes cancer cells to evade the immune system. They have identified a protein that the virus turns off to keep the immune system from eliminating the tumor cells. They are working to identify ways to exploit this finding therapeutically. This project has been very successful in yielding both publications and a NIH R01 grant (direct costs $2,958,357 over 5 years) to Dr. Pyeon entitled “Immune Dysregulation by Human Papillomavirus during Head and Neck Cancer Progression”.

In 2015, Golfers Against Cancer funded Drs. Karam and Jimeno to identify ways to sensitize head and neck cancer cells to radiation therapy. Results from the studies have led to publications and importantly, represent the foundation for a Phase Ib clinical trial opened in the fall of 2016 examining the safety of adding EphB4-ephrinB2 inhibitors to Cetuximab-radiation in the high-risk head and neck cancer population.

Childhood Cancers

While leukemia is the most common childhood cancer, there are several others, most of which can be very challenging to treat.

One childhood cancer with a poor prognosis is called rhabdomyosarcoma (RMS). RMS is a cancer of cells that normally develop into muscle cells. RMS often occurs in children under the age of ten and in teenagers.

In 2013, Golfers Against Cancer funded Drs. Artinger and Ford to develop a new model of RMS. With this model they are able to study the molecular mechanisms of how RMS develops with the long-term goal of identifying new strategies to treat RMS.

In 2015, Golfers Against Cancer funded Drs. Ford and Vibhakar to study new molecularly targeted drugs for a particularly aggressive form of pediatric brain cancer.

General Mechanisms of Cancer Development and Prevention

Cancer is a disease in which cells grow unrestricted, causing damage to surrounding and distant tissues. There are many different types of cancer, but very different cancers can share some of the same molecular mechanisms of tumor development.

In 2010, Golfers Against Cancer funded Drs. Zhao and Zhang to identify chemicals that inhibit a protein that is expressed highly in several cancers, including breast, head and neck, kidney and skin cancers. They screened over 1,000 chemicals and found several that inhibit the protein, and have focused subsequent studies on one of these in particular. They will use this chemical as a starting point to try to make a drug that inhibits this protein to treat cancers.

Golfers Against Cancer funded Drs. Taatjes and Wang in 2012 to study one of the most commonly involved proteins in tumor development called P53. Most tumors rely on P53 to stay alive, so there has been much effort to develop drugs to inhibit its function. This has been a big challenge, though, and to date, no drugs targeting P53 are approved to treat cancer. Drs. Taatjes and Wang have taken a different approach, though, and are trying to identify drugs that inhibit P53’s partners.

In 2015, Golfers Against Cancer funded Drs. Sclafani and Agarwal, to study the use of a natural compound found in red wine, resveratrol, to prevent cancer development.