Funded by the Constellation Gold Network Distributors
Non-small cell lung cancer (NSCLC) is a leading cause of death worldwide. Many NSCLCs are caused by exposure to carcinogens, such as cigarette smoke, which cause changes to a cell’s DNA. These genetic changes can be detected by DNA sequencing methods. Next generation sequencing of tumors can provide clinicians, patients, and researchers with essential knowledge about the genes and proteins that cause and contribute to disease. Unfortunately, most human proteins (>95%) remain undrugged or inaccessible to labeling by FDA approved small molecules. Consequently, most cancer-associated proteins identified by DNA sequencing cannot be drugged. Therefore, we need new methods to identify druggable pockets in cancer-causing proteins. Our research develops such technology. In this study, we will develop a new approach to translate genetic changes into therapies. Our first step is to identify drug vulnerabilities that are specific to tumors. We will achieve this goal by combining next generation sequencing with new proteomics methods developed by our group. Next, we will synthesize drug-like molecules that can specifically label these tumor-associated proteins. Finally, we will determine how the protein targets of our compounds cause or contribute to cancer. Long-term, our studies will help guide the development of new precision therapies that will have fewer side effects and improved patient outcomes.
Abeloff V Scholar* (Tied for Top Rank)
The term “metastasis” describes the spread of cancer cells from their original location in the body to nearby or distant organs. Almost 90% of all cancer deaths are because of metastasis. Unfortunately, this estimate has not changed in the last 50 years and our understanding of metastasis is limited. In order to effectively treat metastasis, we need to first understand them.
Both cancers and their metastasis contain mutations in their DNA. Using our advanced algorithms, we can utilize these mutations to generate a tree that shows the evolution of a cancer in an individual cancer patient. On this tree, we can map the most important changes that can be used by doctors for making treatment decisions. In addition to using individual mutations, we can also use the patterns of all mutations in a cancer patient to pinpoint the processes that were active during evolution of the cancer. Some of these processes can be used as clocks to time the important changes found on the tree.
Overall, we will create a high-definition timeline of the molecular events in the metastatic cancer of each individual cancer patient. The project will examine almost 2,000 cancer patients and increase our understanding of the events needed to transform a cancer to a metastasis. This knowledge is an essential step in providing patients with metastatic cancer with an informed and optimal cancer treatment.
Funded by the Dick Vitale Pediatric Cancer Research Fund
Only half of children with neuroblastoma that is found to be “high-risk” (HR-NB) live after getting the best known treatments. To change this, we need to know what makes HR-NB grow, and find new targets to attack. The New Approaches to Neuroblastoma Therapy (NANT) (www.nant.org) is a team of doctors working with patients and/or in labs to find new treatment ideas and test them in children whose tumor didn’t go away after getting the best known treatments. If NANT’s new treatments are safe and make some tumors get smaller, they are then tested in more children to see if the new treatment is better than the best-known treatments. A little blood, bone marrow, and tumor are also taken from patients on NANT treatments to study in labs to see why our new idea did or didn’t work, and how we can make them better. There are 18 NANT hospitals in the United States, Canada, Australia, and Europe. NANT is the only group working only on new/better HR-NB treatments. This grant will support NANT doctors, labs, and the people who work in the NANT office to quickly take new ideas from labs and turn them into treatments being given to children with HR-NB. It also helps us to store patient samples so they can be used to keep finding new and better ideas. Our goal is to find safe treatments that will help more children with HR-NB to live.
Funded in partnership with the Goldberg Family Foundation
We need better tools to screen for and diagnose cancer earlier and at a curable stage in individuals that carry inherited mutations such as BRCA1/2 and other cancer susceptibility genes that put them at high risk for breast, ovarian, prostate, pancreatic and other cancers. We propose to use powerful new approaches for “next-generation” DNA sequencing from standard blood samples to identify circulating tumor DNA mutations as a very sensitive marker of early cancers in high-risk individuals. These “liquid biopsies” may prove to be a far easier and more sensitive way to screen for cancer than our current imaging based approaches using mammograms, MRI’s, etc. To this end, we have been collecting blood samples from our genetically high-risk patients with and without cancer, and before and after prophylactic or cancer surgeries, for liquid-biopsy analyses using technology developed at Stanford.
Funded by Hooters of America, LLC
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.
Funded by the Gastric Cancer Foundation
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 a set 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 aberrant additions cause cancer. To answer this question, it is crucial to know all the interaction targets for the additions in cancer cells. But no method has been made 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 particular member in this group will be chosen for this work. Because it shows much higher activities in diverse types of cancer. The full range of interacting targets for this protein will be clearly determined. Moreover, the patterns and levels of such interactions in cancer cells can be precisely measured by our creative approach. These findings will unveil the interaction networks of this cancerous protein to guide our further studies. The fundamental knowledge obtained from this work will advance our understanding of cancer. Importantly, it will foster the development 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.
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