Understanding the Role of p53 in the Development and Progression of Oligometastatic Castration-Sensitive Prostate Cancer

Project Details

Description

Scientific Objectives/Rational: Prostate cancer represents the third most commonly diagnosed cancer in the United States and results in greater than 30,000 deaths per year, most of which are due to metastatic disease. Thus, great efforts are needed to improve outcomes for these patients. Historically, metastatic disease has been treated with systemic therapies such as chemotherapy, or in the case of prostate cancer, androgen deprivation therapy, also known as hormone therapy, which are drugs that travel and treat cancer throughout the body.

Local therapies, such as radiation or surgery, have historically not been used in the treatment of metastatic disease. However, in order to improve outcomes for prostate cancer patients, there has been increasing interest at integrating local therapies into the treatment paradigm of metastatic disease, especially oligometastatic disease, typically defined as patients with = 5 metastatic lesions. Recent clinical trials, including from our research group, have demonstrated the integration of radiation in the treatment oligometastatic lesions delays progression of disease and can also delay the need to initiate androgen deprivation therapy and its unfavorable side effects. While the use of radiation therapy to treat metastatic disease appears promising, we still do not have a good understanding of which patients most benefit from this treatment. Our research group has generated preliminary evidence that the underlying genetic mutations of a tumor might be able to help predict which patients derive the greatest benefit from this type of treatment. Additionally, our research team has also identified a specific gene, TP53, which appears to be important and related to oligometastatic prostate cancer progression and metastasis. With this background, we propose the following goals:

(1) Validate the utility of genetics in predicting response to radiation in oligometastatic prostate cancer.

(2) Study the importance of TP53 in the progression of oligometastatic prostate cancer using cells and animal models.

(3) Study whether treatment with a drug targeting TP53 can halt progression in oligometastatic prostate cancer.

Impact for Patients: The proposed work will impact patients from several angles. First, given the (1) accumulating evidence that radiating metastatic lesions can delay time to tumor progression, and (2) our preliminary evidence that tumor genetics can provide predictive information regarding who most benefits from radiation treatment, validation of these findings can result in an immediate impact on patients and influence treatment decisions. Second, identifying a group of patients who most benefit from radiation therapy may allow for delays in the initiation of androgen deprivation therapy, also known as hormone therapy, which can significantly improve quality of life for these patients by avoiding the often-unpleasant side effects that are associated with this type of treatment. In the long term, a better understanding the role of TP53 in the progression of oligometastatic prostate cancer can allow for new therapeutic avenues for patients. We will specifically evaluate whether pharmacologic targeting of TP53 is feasible in prostate cancer and whether it can delay the progression of metastatic disease. Thus, this information can lead to new treatment paradigms that might be able to integrate drug therapy with radiation of metastatic lesions in the treatment of prostate cancer.

Career Goals: I have spent the last 4 years at Johns Hopkins completing my medical training as an oncologist. I will now join the faculty at Rutgers University and Robert Wood Johnson Medical School. My career goals are twofold: (1) serve the community I grew up in as an oncologist and (2) become a physician scientist engaged in research aimed at improving the lives of individuals with cancer. My passion in research is prostate cancer, and I have focused the last five years of my training on this topic resulting in much of the preliminary data that forms the basis of this proposal. Being awarded this grant will allow me to achieve my career goals by (1) providing me additional mentorship during my transition to new junior faculty, and (2) provide me with the support in terms of funding and protected research time to carry out the proposed work.

StatusActive
Effective start/end date1/1/21 → …

Funding

  • Congressionally Directed Medical Research Programs: $1,177,437.00

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