Precision cancer medicine refers to the tailoring and targeting of cancer treatment to the individual characteristics of each patient. Triple negative breast cancers (TNBC), specific types of breast cancer, are known to be very aggressive and tend to occur more frequently in Hispanic than non-Hispanic white patients. A team of researchers at the UC San Diego Moores Cancer Center was formed to investigate the development of treatments that will target TNBC. This research will include the setup of clinical trials–research studies that test how well certain treatments work in patients with cancer. It is well known that there are obstacles that prohibit racial/ethnic minorities from participating in clinical trials. These include a variety of factors related to the patient, his/her provider, and the health system where he/she receives medical care. The goal of this application is to leverage work in a precision medicine project to engage with community partners on the topic of clinical trial accrual. This will be accomplished by addressing the following specific aims, focusing on Hispanic communities in San Diego and Imperial counties: 1) Assess the unique community perspective and experience of Hispanic breast cancer patients related to clinical trials; and 2) Educate community partners in precision medicine, clinical trials, patient perspective and experience, and the importance of minority representation in research. The proposed work will be conducted under the UC San Diego Moores Cancer Center’s Community Outreach and Engagement, led by an expert team of investigators, physicians, and disparities researchers and staff.
Project 1: My research interest is cancer genetics with an emphasis on clinically relevant questions that will improve our understanding of the cancer genetics of clinical phenotype and simultaneously improve patient care in oncology. I have extensive bench research experience in the fields of genome sequencing technology development, human genetic analysis through human genome sequencing and molecular assay development. My research benefits from the various innovations in genomic and genetic technologies that my group has developed.
Project 2: Based on a series of recent discoveries using cutting edge tools in genomics, we have (1) identified a new targeted way of treating metastatic gastric cancer and (2) pioneered a new way of determining how gastric cancer cells control normal cells in the surrounding stomach tissue.
Our overall goal for this project is to use single cell genomic sequencing to identify new drug targets by analyzing primary gastric cancers from metastatic patients.
Project 3: Based on a series of recent discoveries using cutting edge tools in genomics, we have (1) identified a new targeted way of treating metastatic gastric cancer and (2) pioneered a new way of determining how gastric cancer cells control normal cells in the surrounding stomach tissue.
Our overall goal for this project is to determine if our new discovery of a drug combination will improve the treatment of metastatic gastric cancers with the FGFR2 defect.
Funded in partnership with the Goldberg Family Foundation and in collaboration with the Gray Foundation
Individuals with BRCA1 or BRCA2 mutations have an increased risk of developing breast, ovarian, pancreas, prostate and other types of cancer. Tumors arising in these individuals are often sensitive to PARP inhibitors (PARPi) and this class of drugs has shown remarkable success in the treatment of BRCA1 and BRCA2-mutant tumors. Despite these successes, tumors frequently become resistant to therapy. Using functional genomic approaches, we will investigate mechanisms of resistance and identify novel genetic vulnerabilities that can be exploited by PARPi treatment. We will also investigate the immune response to BRCA-mutant tumors and explore ways to improve the ability of immune cells to recognize and kill these tumors. The ultimate goal of these studies is to improve outcomes for patients with BRCA-mutant tumors and to identify new groups of patients that can benefit from PARPi.
Funded by the Stuart Scott Memorial Cancer Research Fund
Stem cell transplantation is an effective way to treat patients with blood cancers. However, this treatment can cause short- and long-term side effects. These side effects may affect quality of life and increase risks for other diseases. Doctors must balance these risks with the potential for stem cell transplant to cure patients. A risk-prediction model can help with such decisions, but current models are inadequate. Risk-prediction models are often based on a patient’s age, but people of the same age in years may not be alike in terms of underlying health. Underlying health can be estimated with various “biomarkers.” Our proposal is designed to identify a new biomarker that shows whether a patient is fit for stem cell transplant. We are studying clonal hematopoiesis of indeterminate potential (CHIP), a group of genes that indicate the health of a patient’s blood cells. Our hypothesis is that patients with CHIP in the blood before stem cell transplant will have poor outcomes after transplant. To test this, we will use a large collection of blood samples taken from blood cancer patients before stem cell transplant. We also have information about each patient’s health after transplant. We will use DNA sequencing to measure CHIP genes in the blood samples. We will use statistics to compare CHIP in the samples with patient health after stem cell transplant. If these correlate, it will show that CHIP is a good biomarker for use in a risk-prediction model. This will help doctors make personalized decisions that improve the lives of blood cancer patients.
V Scholar Plus Award – extended funding for exceptional V Scholars
Cancer cells contain aset of highly active proteins. They can add small groups to a series of target proteins. These uncommon additions are often linked with tumors found in breast, liver, and other tissues. To date, it is still unclear how those aberrantadditions cause cancer. To answer this question, it is crucial to know all the interactiontargets for the additions in cancer cells. But no method has beenmade available to resolve this key issue. In this project we are aimed to create an innovative platform to achieve this goal. Our research plan will use chemistry and biotechnology to make new tools for target identification. A particularmember in this group will be chosen for this work. Because it showsmuch higher activities indiversetypes of cancer. The full range ofinteracting targets for this proteinwill be clearly determined. Moreover, the patterns and levels of such interactionsin cancer cells can be precisely measured by our creative approach. These findings willunveil the interaction networks of this cancerous protein to guide our further studies. The fundamental knowledge obtained from this workwill advance our understanding of cancer. Importantly,it will foster thedevelopment of new approaches for cancer detection and treatment.
V Scholar Plus Award – extended funding for exceptional V Scholars
Cure rates for childhood leukemia have considerably improved in the last few years. Despite this, there are certain sub-sets of leukemia that do not respond well to current therapies.Currently used treatments are often extremely aggressive and non-specific, leading to significant debilitating effects in these patients. The overall objective of this application is to validate exciting new therapeutic targets that we have identified in high-risk subsets of AML using genetic and chemical approaches.
The reasons why cancer patients do or do not participate in cancer (clinical trials) research are complex. Often this is due to the lack of awareness of which studies are occurring by both the patient and their primary care clinicians. Another very important reason is that patients, especially patients that do not speak English, are not invited to participate because the research team does not have non-English speakers or study materials in the patient’s language. We at the UC San Diego Moores Cancer Center (MCC) have the opportunity to better understand and address low clinical trials participation among our largest under-represented racial/ethnic group, Hispanics. Working with a multidisciplinary team of physicians and non-physician scientists, we propose to 1.) Educate community providers about breast cancer trials at MCC, and 2.) Assess specific interests and needs among the MCC breast cancer team, and combine this with existing evidence, including interview findings (knowledge and Hispanic from a recent (2016) V Foundation grant), to develop and implement minority clinical trial accrual training for the MCC breast cancer team. By focusing on minority breast cancer patients, V Foundation funds complement and expand our emerging efforts to increase minority clinical trials enrollment (accrual) and related outreach and inform how to intervene with MCC patients, providers, and leadership. We are particularly interested in targeting Hispanic breast cancer patients because they are the largest minority group in San Diego County, the region served by the MCC.
Of the cancers that affect both men and women, colon cancer is the second leading cause of cancer deaths and the third most commonly diagnosed cancer in the United States. Interestingly, evidence from the clinic links disruption of normal 24-hour rhythms with many diseases including a higher risk of cancer. Our internal clock controls sleep/wake cycles, feeding and metabolism and disruption of the clock has been reported in several cancer types, including colon cancer. Yet, the precise process of clock disruption in colon cancer remains undefined. We are interested in cells that have the ability to initiate tumors because these cells have been found to be treatment resistant. We propose to determine how loss of the clock can promote colon cancer by changing the cues that direct these cells that initiate cancer. To accomplish this, we have generated a mouse model to understand the effects of clock disruption on cell growth in the intestine. We propose that disruption of both the clock and loss of cues that control normal cells in the intestine can result in colon cancer. The goal of these studies is to provide new directions towards clock-dependent treatments that can target colon cancer.
Vintner Grant funded by the 2018 V Foundation Wine Celebration in honor of Karen Aldoroty
Immunotherapy is a very promising new treatment that uses the body’s own immune system to recognize and fight cancer. This research project focuses on immune cells called macrophages, which are a group of white blood cells in the body. Previous studies have showed that when cancer cells grow in the body, they use signals to protect themselves and escape from macrophages. When treatment was given to block these signals, macrophages were able to recognize and attack cancer cells. In the tumors, in addition to cancer cells, there are many other groups of cells including macrophages. Cancer cells can travel from the primary tumors and grow in organs such as the lung, liver and brain. This caused over 90% of cancer patient deaths. Importantly, these organs also have many macrophages. It is very important to examine if and how macrophages can be used to defend against tumor cells and thus to treat cancer. However, there is much that we do not understand about what exactly occurs during these processes. In this study, we would like to understand how macrophages and cancer cells interact with each other and how macrophages decide if or not they should attack tumor cells. This knowledge will be used to develop new immunotherapies that block cancer cells’ protective traits and allow macrophages to attack and clear them.
Lung cancers are often driven by genetic changes. The focus of my research is on a type of lung cancer that is driven by changes in the EGFR gene. This type of lung cancer often occurs in younger patients who are non-smokers. New medications can target these changes. This has allowed patients to live longer. However, patients are almost never cured of their disease. My goal is to understand why responses to these EGFR targeted treatments are almost never curative. Then I will work to identify new medications that can be used together with EGFR inhibitors. This may allow patients to live longer. I will accomplish this goal by identifying all of the genetic changes present in patients’ tumors. This will allow us to understand which ones may be allowing cancer cells to survive. I will also assess tumors for other changes that occur within cancer cells. In addition, I will look at the immune cells that are in the tumor. To summarize, the goal of this research is to identify new combination therapy strategies that can improve the depth and duration of response to EGFR targeted therapies, allowing patients with this deadly disease to live longer.
