Nuclear ErbB3 Predicts Sensitivity to Androgen Receptor Inhibitors in Castration-Resistant Prostate Cancer
Abstract
The scientific objective for the proposed project is to determine whether a particular protein, called ErbB3, that is found in prostate tumors can tell us whether a patient with prostate cancer will benefit from a type of treatment called “AR inhibitors.” The scientific rationale for the proposed project is that the presence of ErbB3 in the patient’s prostate tumor makes the tumor respond better or worse to the “AR inhibitors” that are typically given to a prostate cancer patient. The ultimate applicability of this research is that it may prevent patients from unnecessarily being given AR inhibitors, which are both toxic to the patient’s body and expensive for the healthcare system and can instead help determine which medication will work best in treating the patient’s prostate cancer. This study aims to contribute to “Define the biology of lethal prostate cancer,” as stated in the FY20 PCRP Overarching Challenges. It may also contribute to “Develop treatments that improve outcomes for men with lethal prostate cancer,” which is another FY20 PCRP Overarching Challenge. The results of this study will help patients who are no longer responding to “first-line” treatment (typically hormonal treatment) and are being considered for treatment with AR inhibitors (targeted drugs), of which there are three that are currently Food and Drug Administration-approved and available. It can also help patients after they have undergone surgery (to remove part or all of the prostate that contains the tumor), but before they are given first-line therapy. The clinical benefit to patients is that they will be spared the significant physical toxicity and emotional and financial burden that accompany first-line therapy and AR inhibitors. Patients may also enjoy a longer life, with improved quality-of-life, because their bodies are not exposed to the drugs’ side effects. The risk is that, while some patients will respond to these AR inhibitors, there may be those who do not. This is because there may be other proteins or factors that make their tumor resistant to treatment, and those reasons fall outside the scope of this proposed research. The projected time it may take to achieve a widespread patient-related outcome could be between 5 and 10 years, and the fact that this proposed research will use a patient blood sample to achieve these results means that there may be no need for a painful biopsy – in fact, since prostate cancer patients undergo frequent blood tests to monitor their PSA level (prostate-specific antigen), either part of the same blood sample could be used or a few additional milliliters of blood may be drawn during the same doctor’s visit. This can save the patient and their doctor time and effort because there are instances when Veteran patients must travel great distances for their doctor’s appointments. The Principal Investigator’s (PI’s) career goal is to become an independently funded researcher in the field of prostate cancer. This could be as a professor at a research-intensive university (ideally one that has a teaching hospital affiliated with itself) or as a senior scientist in a not-for-profit research institution. To this end, the PI has presented a Researcher Development Plan that includes mentorship and training in current experimental techniques (such a next-generation sequencing, which are helping us understand genes and disease so that we can use precision medicine to treat patients) and data analysis from three professors who have extensive experience in the field of prostate cancer research themselves. They have also mentored numerous graduate students, post-doctoral trainees (such as the PI) and junior faculty over the years and so are well-equipped to help the PI embark on an independent research career.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 05, 2021
- Source ID
- W81XWH2110073
Entities
People
- Maitreyee Jathal
Organizations
- United States Army
- University of California, Davis