Pedal the Cause Research Grants

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Impact of Fundraising

100% of the proceeds from Padres Pedal the Cause stay in San Diego to fund life saving cancer research projects conducted by our beneficiaries: Moores Cancer Center at UC San Diego Health, Sanford Burnham Prebys Medical Discovery Institute and The Salk Institute for Biological Studies and Rady Children’s Hospital–San Diego. Over the past three years, the Padres Pedal community has funded 16 groundbreaking, collaborative research projects. The research that gets funded through Padres Pedal grants is collaborative and translational and focuses on finding new treatments and prevention for many different types of cancer.

Following are summaries of all the research projects funded by Padres Pedal.

2015 GRANTS

Research Focus: Targeting KRAS Mutant lung cancer with biphosphonated/statins and rapamycin analogs

Type of Cancer: Lung

Awardees:

  • Lyudmila Bazhenova, MD (Moores Cancer Center at UC San Diego Health)
  • Inder Verma, PhD (Salk Institute Cancer Center)

Lung cancer is the most common human malignancy and leads to about one-third of all cancer-related deaths. There are three major genetic mutations found in lung cancers: EGFR, EML4-ALK and KRAS. The latter, KRAS, is more common in Caucasians, males and smokers, and does not currently have good therapeutic options. Previous studies have shown that select drugs prescribed for bone resorption, when used in combination with rapamycin (an immunosuppressant commonly used to prevent the body from rejecting organ and bone marrow transplants), could successfully prevent tumor growth and prolong survival. PEDAL15 grant funding will allow scientists to test the drug combination in metastatic lung tumors with KRAS mutations, as well as decipher what makes a tumor more sensitive to this drug combination. Additionally, it has been found that certain drugs designed to lower blood cholesterol (statins) could also inhibit protein modification. This grant will make it possible for scientists to test combinations of statins with rapamycin. Scientists hope to develop a viable combination therapy to combat lung cancers with KRAS mutations and demonstrate the power of immediate translation of results into the clinic.

 

Research Focus: The GNAS-PKA Onco-Signaling Network in Colorectal Malignancies

Type of Cancer: Colorectal

Awardees:

  • Silvio Gutkind, PhD (Moores Cancer Center at UC San Diego Health)
  • Susan Taylor, PhD (Moores Cancer Center at UC San Diego Health)
  • Tony Hunter, PhD (Salk Institute Cancer Center)

Every year, more than 135,000 Americans – and 1.35 million people worldwide – are diagnosed with colorectal cancer. With 50,000 deaths each year, colorectal cancer is the second leading cause of cancer deaths in the United States. New approaches are clearly needed to explain the underlying biology of colorectal cancer, which will help the development of new and more effective options to prevent and treat this highly prevalent human malignancy. Aspirin and multiple over the counter non-steroidal anti-inflammatory drugs are effective in preventing colorectal cancer, supporting that chronic inflammation contributes to the development of this cancer. A molecule known as Protein Kinase A (PKA) is often stimulated by inflammatory mediators in the normal intestine and colorectal tumors. Through PEDAL15 funding, scientists will be able to study what causes the unrestrained activation of PKA in colorectal cancer and how PKA then stimulates cancer growth. It is believed that these studies will increase our understanding of colorectal cancer initiation and progression, will help identify patients at risk of developing this malignancy, and will reveal new therapies to prevent and treat this disease.

 

Research Focus: Epigenetic Basis of Platinum Drug-resistance in Ovarian Cancer

Type of Cancer: Ovarian

Awardees:

  • Olivier Harismendy, PhD (Moores Cancer Center at UC San Diego Health)
  • Stephen Howell, MD (Moores Cancer Center at UC San Diego Health)
  • Joseph Ecker, PhD (Salk Institute Cancer Center)

The majority of patients treated for ovarian cancer receive platinum-based chemotherapy, but 85 percent of patients who initially responded will eventually relapse with a recurrent tumor that is resistant to treatment. Platinum drug resistance is a serious clinical problem affecting thousands of patients every year. With the modern tools of precision medicine and genomics, scientists now have a chance to better understand how tumor cells adapt to and escape the treatment. PEDAL15 funding will allow scientists to apply an experimental system developed to obtain platinum sensitive and resistant cells that have an identical DNA sequence. Scientists will evaluate why tumors can rapidly adapt to treatment and become resistant. This research is likely to predict why certain ovarian tumors are more likely to become resistant and how soon. It may also lead to the identification of therapies to prevent or delay the onset of platinum resistance.

 

Research Focus: KRAS Addiction and Protein Biomarkers of Response to Anti-KRAS Therapy in NSCLC Patient-derived Xenografts

Type of Cancer: Lung

Awardees:

  • Hatim Husain, MD (Moores Cancer Center at UC San Diego Health)
  • Garth Powis, DPhil (Sanford Burnham Prebys Cancer Center)

In approximately 25 percent of lung cancer cases, the gene KRAS may be mutated. Therapies for patients who have a KRAS mutation are not currently approved by the United States Food and Drug Administration. This challenge remains a largely unmet need among lung cancer patients. Every year an estimated 39,000 people will die of this molecular form of the disease. In this PEDAL-funded project, scientists will study proteins that are expressed in these tumors and seek to identify additional markers that may be used to determine who will respond to novel KRAS-directed therapies. Additionally, the funding will also facilitate the study of new drug therapies developed to target the KRAS protein complex and test its efficacy in KRAS-mutated and pathway dependent cancer cells. This groundbreaking research could serve the basis of a future clinical trial to evaluate a new anti-KRAS drug for patients with KRAS mutations and pathway dependency.

 

Research Focus: Mechanisms Linking Prolonged Nightly Fasting with Cancer Risk

Type of Cancer: All Cancers

Awardees:

  • Ruth Patterson, PhD (Moores Cancer Center at UC San Diego Health)
  • Dorothy Sears, PhD (Moores Cancer Center at UC San Diego Health)
  • Satchidananda Panda, PhD (Salk Institute Cancer Center)

Obesity is an epidemic. Identification and validation of feasible, effective approaches to reduce obesity-related cancer risk is needed. Research studies indicate that time-restricted feeding can protect against obesity, high insulin levels, fatty liver, and inflammation – all of which can increase cancer risk. Through this PEDAL15-funded study, researchers will test whether, in comparison to a short fasting interval, a 13-hour or greater nightly fasting interval is associated with lower blood glucose levels, lower inflammation, lower levels of obesity, and improved sleep. Scientists will also investigate the association of prolonged nightly fasting with metabolites in the blood, such as sugars and fats, and the association of nightly fasting with the gut microbiome (a collection of all microorganisms and viruses that live in the intestines). If habitual prolonged nightly fasting improves metabolic health and reduces obesity-related cancer risks, this would be a crucial discovery in the prevention of cancer in adults.

 

Research Focus: Targeting Stem Cell Signals in Cancer Development & Progression

Type of Cancer: All Cancers

Awardees:

  • Tannishtha Reya, PhD (Moores Cancer Center at UC San Diego Health)
  • Michael Jackson, PhD (Sanford Burnham Prebys Cancer Center)

To identify new therapeutic targets for cancer, researchers have focused on stem cell programs that are reactivated in cancer. It has been demonstrated that the stem cell signal Musashi (Msi) is highly upregulated during leukemia development and that its blockage can prevent tumor growth and progression. Data suggests that targeting Msi may provide a new strategy for therapy. To move this work forward to the clinic, PEDAL15 grant funding will be used to develop inhibitors of Msi and test their effectiveness against cancer growth. Outcomes from this study have the potential to identify a new class of therapeutics for cancers that are largely unresponsive to current therapies.

 

Research Focus: Detecting Correlates of Vaccine Responses in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Type of Cancer: All Cancers

Awardees:

  • Randy Taplitz, PhD (Moores Cancer Center at UC San Diego Health)
  • Shane Crotty, PhD La Jolla Institute for Allergy and Immunology

Vaccines decrease the risk of infection by working with the body’s natural defenses to develop immunity or protection against disease. Patients with cancer and other diseases affecting the immune system may lose immunity to those diseases against which they have previously been vaccinated and also may have reduced ability to develop immunity to a new vaccination. Hematopoietic cell transplant (HCT) is a procedure that replaces defective or damaged cells in patients whose normal blood cells have been affected by cancer. PEDAL15 funds will allow scientists to measure vaccine-specific immunity before and after vaccination with the pneumococcal and Tdap vaccines, which are given at standardized times in the year after HCT. Ultimately, this effort is expected to lead to better vaccination strategies which will in turn lead to decreased infections due to vaccine-preventable diseases in this vulnerable patient population, as well as contribute to our understanding of immune recovery after HCT.

 

2014 GRANTS

Research Focus: Highly selective, synthetic, cleavage specificity- based nanobiosensors for tumorigenic and anti- tumorigenic MMPs

Type of Cancer: All Cancers

Awardees:

  • Alex Strongin, PhD (SBMRI)
  • Shu Chien, MD, PhD (Moores Cancer Center)

There is consensus among professionals that matrix metalloproteinases (MMPs), the specialized enzymes produced in cancer, are a promising drug target. Despite the urgent need and significant value for cancer patients, MMP biosensors are currently unavailable. As a result, physicians are blindfolded and incapable of selecting optimal treatment regiments for patients. To overcome these deficiencies, researchers will now be able to test the unique fully-synthetic nanobiosensors which allow the read-out of the individual MMPs in cells/tissues.

As a result of this work, clinicians will be armed with a multitude of novel diagnostic/prognostic molecular tools, which can then be used to rationally design a knowledge-based personalized medicine treatment for the individual patients.

 

Research Focus: Cytotoxic Breast Cancer Treatment Effects on Aging

Type of Cancer: Breast Cancer

Awardees:

  • Deborah Kado, MD, MS (Moores Cancer Center)
  • Jan Karlseder, PhD (Salk)

With a growing aging U.S. population and an expected increase in cancer survivorship projected to affect more than 60 percent of those over the age of 65, there is concern that the effects of cancer treatments on physiologic reserve may carry long-term undesirable health consequences. Whether accelerated aging affects patients diagnosed with breast cancer, the most common type of cancer to affect women, is unknown. As a result of this grant, a multi- disciplinary team of scientists, clinicians, geriatricians and cancer physician specialists will conduct an integrated effort to understand what anti-cancer therapies do, not only with respect to healthy cells, but also to overall health and function. Our ultimate goal is to better understand whether or not chemotherapy may contribute to accelerated aging in breast cancer patients, and if so, identify and target modifiable factors to decrease the risk of not only developing recurrence, but also to maximize long-term healthy function and quality of life in these women as they age.

 

Research Focus: In Vivo Modeling of Anti- Tumor Responses of Human Melanoma Patients and Their Responses to Checkpoint Immunotherapy

Type of Cancer: Melanoma Cancer

Awardees:

  • Linda Bradley, PhD (SBMRI)
  • Greg Daniels, MD, PhD (Moores Cancer Center)

Melanoma skin cancer is a deadly disease that kills many patients after the cancer spreads. Current therapies are not effective, and many patients have very few treatment options after metastasis occurs. Recently, immunotherapies have been developed to augment immune cell function to kill tumors. Even though these immunotherapies are effective in some patients, many others are nonresponsive. There is therefore a pressing need to predict whether a patient will or will not respond to these drugs so that effective personalized treatment options can be offered. Pedal-funded research will allow scientists to test a patient’s immune system against their tumors to determine whether they will have a productive response with clinically available drugs. These studies will be highly significant because if they show promise in melanoma, these tools can be further applied to combat other cancers in humans.

 

Research Focus: Therapeutic Reprogramming of Pancreatic Cancer Stroma Via Modulation of p 62 and p 53

Type of Cancer: Pancreatic Cancer

Awardees:

  • Andrew Lowy, MD (Moores Cancer Center)
  • Geoff Wahl, PhD (Salk)
  • Comiso Commisso, PhD (SBMRI)
  • Jorge Moscat, PhD (SBMRI)

Pancreatic cancer remains the most deadly common cancer in the U.S. with a five-year survival rate of 6 percent. Despite the fact that fewer persons are diagnosed with pancreatic cancer than many other cancers, this high death rate will likely make it the No. 2 cancer killer by 2020.

Researchers have identified that non-cancerous cells present in pancreatic tumors have lost the function of two critical proteins that normally act to suppress cancer development. This grant will allow new tools to be developed by researchers to rapidly screen through a very large number of drugs in order to identify those which can restore the function of these proteins. By identifying such drugs, they can then be tested as part of a new treatment approach to pancreatic cancer.

“There is a misconception that cancer research projects take years – even decades – to make a lasting impact,” said Garth Powis, DPhil, Director of Sanford- Burnham Cancer Center. “Pedal the Cause is fast-tracking that process. After just one year, research funded by Pedal has led to breakthrough findings significant enough to receive additional funding and sponsorship by the NIH. We are thrilled. It’s Pedal-powered progress.”

 

2013 GRANTS

Research Focus: Finding New Hereditary Breast Cancer Markers

Type of Cancer: Breast Cancer

Awardees:

  • Lisa Madlensky, PhD, (Moores Cancer Center)
  • Geoffrey Wahl, PhD, (Salk)

Only 10 percent of breast cancer cases are linked to BRCA. Lisa Madlensky, PhD, (Moores Cancer Center) and Geoffrey Wahl, PhD, (Salk) are working with a family that is strongly suspected of carrying a hereditary breast cancer gene, even though all members are BRCA-negative. The study aims to find a new susceptibility gene for which families with unexplained hereditary breast cancer can be tested. This information could help determine which family members have the gene and therefore need to be monitored carefully or undertake breast cancer prevention measures, and which family members did not inherit the gene and are considered to be at average risk.

 

Research Focus: Stopping Cancer Growth

Type of Cancer: All Cancers

Awardees:

  • Seth Field, MD, PhD, (UC San Diego)
  • Michael Jackson, PhD, (Sanford-Burnham)

The process of secretion by which cells export proteins was not previously known to play an important role in cancer. However, a newly discovered pathway that functions in secretion, named for its key protein GOLPH3, drives a high fraction of cancers that together account for the majority of cancer deaths, making an unprecedented link between secretion and cancer. Seth Field, MD, PhD, (UC San Diego) and Michael Jackson, PhD, (Sanford-Burnham) will collaborate on research to take advantage of this unique pathway as a target for a new class of cancer treatments. They will identify inhibitors of the GOLPH3 pathway to study their potential as novel cancer drugs.

 

Research Focus: Reprogramming Pancreatic Cancer’s Hard Shell

Type of Cancer: Pancreatic Cancer

Awardees:

  • Andrew Lowy, MD, (Moores Cancer Center)
  • Geoffrey Wahl, PhD, (Salk)

Every day, a San Diegan will be diagnosed with pancreatic cancer, yet only one in 20 will survive for five years after this diagnosis. Pancreatic cancer is the fourth deadliest cancer, yet very little progress has been made in fighting the disease over the last 50 years. Pancreatic cancer is difficult to treat in part because the cancer grows encased in a thick tissue protective layer called the “activated stroma.” Andrew Lowy, MD, (Moores Cancer Center) and Geoffrey Wahl, PhD, (Salk) will study a novel way to treat this recalcitrant cancer by focusing on smart-drugs that can reprogram the stroma to allow other smart-drugs to attack the cancer inside.

 

Research Focus: Halting Breast Cancer’s Spread

Type of Cancer: Breast Cancer

Awardees:

  • Michael Karin, PhD, (Moores Cancer Center)
  • Geoffrey Wahl, PhD, (Salk)

The spread of cancer cells from the primary tumor to distant organs, termed metastasis, is the leading cause of cancer-related death. Even the removal of early-diagnosed primary breast cancer cannot guarantee prevention of metastatic recurrence many years later. Michael Karin, PhD, (Moores Cancer Center) and Geoffrey Wahl, PhD, (Salk) will research ways of halting breast cancer metastasis by inhibiting Ubc13 and p38, enzymes involved in controlling metastatic spread..

 

Research Focus: Discovering Gastrointestinal Stromal Tumor Weaknesses

Type of Cancer: Gastrointestinal Cancer

Awardees:

  • Jason Sicklick, MD, (Moores Cancer Center)
  • Robert Weschler-Reya, PhD, (Sanford-Burnham)

Gastrointestinal stromal tumor (GIST) is a cancer that arises from nerve cells that control the movement of muscles in the intestine. Many GISTs have a high level of a protein called KIT, which led to the use of a drug called imatinib that could attack KIT. This became the first targeted, personalized treatment of solid tumors. However, it did not completely cure the disease, because some GISTs don’t have the KIT target or develop a drug-resistant form of KIT. Jason Sicklick, MD, (Moores Cancer Center) and Robert Weschler-Reya, PhD, (Sanford-Burnham) will use advanced screening technology to discover new drugs that can target GISTs resistant to current therapies.