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2020 Advanced Accelerated Applications-PCF Young Investigator Award

Alok Tewari, MD, PhD

Harvard University/Dana-Farber Cancer Institute

Mentors: Eliezer Van Allen, MD; Myles Brown, MD; Mary-Ellen Taplin, MD

Integrated Single-Cell Analysis of Mechanisms of Therapeutic Resistance in Prostate Cancer Patients

Description:

  • High-risk localized prostate cancer is associated with a significant risk of disease progression and prostate-cancer specific mortality. Efforts are underway to develop new treatment strategies to improve outcomes in these patients.
  • Recent phase 2 trials of neoadjuvant (prior to surgery) anti-androgen therapies including enzalutamide, apalutamide and/or abiraterone with standard androgen deprivation therapy (ADT) for six months, followed by prostatectomy, have had highly promising results. These studies have led to an ongoing phase 3 trial testing combination anti-androgen neoadjuvant therapy before prostatectomy for high-risk localized prostate cancer.
  • Dr. Alok Tewari is studying the biological impact of intense anti-androgen neoadjuvant therapy in patients with high-risk localized prostate cancer.
  • In this project, Dr. Tewari will perform comprehensive molecular analyses of samples from patients treated with intense anti-androgen neoadjuvant therapy as well as from rapid autopsy samples from advanced disease to identify common and divergent mechanisms and biomarkers of treatment response vs. resistance.
  • Dr. Tewari will also leverage multi-platform analysis of rapid autopsy samples to study mechanisms of resistance to other therapies including radiopharmaceuticals in advanced prostate cancer.
  • If successful, this project will determine why neoadjuvant hormonal therapy works for some patients but not in others, identify predictive biomarkers for appropriate treatment selection in high-risk patients and uncover tumor and microenvironmental mediators of resistance and response to therapies such as radiopharmaceuticals in advanced disease.

What this means to patients: Dr. Tewari is investigating molecular mechanisms and biomarkers of response vs. resistance to intense anti-androgen neoadjuvant therapy, radiopharmaceuticals, and other treatments.  This will result in improved selection of patients who will benefit from these treatments and potentially inform drug development efforts to improve the chance of cure for patients with prostate cancer.