Tom Beer, M.D.

Tomasz M. (Tom) Beer, M.D.

Research Accomplishments

Androgen-receptor targeted treatments for advanced prostate cancer. Androgen signaling is a critical driver of prostate cancer progression therefore potent and selective inhibitors of androgen synthesis and androgen receptor signaling that overcome resistance to previously used agents were developed and their impact was defined through phase I, phase II and global phase III trials that established new standards of care for prostate cancer. Ongoing work focuses refining their role in the treatment of patients and on in vivo discovery of mechanisms of resistance to the next generation of androgen signaling inhibitors.

Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 2009

Antitumor Activity of MDV3100 in Castration-Resistant Prostate Cancer: a Phase I-2 Study. Lancet 2010

Enzalutamide in metastatic prostate cancer before chemotherapy. New England Journal of Medicine 2014

Updated Interim Efficacy Analysis and Long-term Safety of Abiraterone Acetate in Metastatic Castration-resistant Prostate Cancer Patients Without Prior Chemotherapy (COU-AA-302). European Urology 2014

Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncology 2015

All androgen receptor targeted therapy papers
Immunotherapy for prostate cancer. Harnessing the immune system to combat cancer is increasing becoming a reality. Following the phase I/II evaluation of the CTLA-4 antibody ipilimumab that demonstrated that tumor antigen-agnostic immunotherapy results in tumor responses in prostate cancer, the agent was examined in two pivotal phase III clinical trial. Recently, significant anti-tumor activity with the PD-1 inhibitor pembrolizumab in combination with enzalutamide was demonstrated. We also made contributions to the studies of cellular immunotherapy with the national randomized P-11 trial demonstrating that immunotherapy may slow the rate of rise in serum PSA in patients with post-operative biochemical relapse. Current work focuses the phase III evaluation of the novel dendritic cell vaccine DCVAC/PCa.

Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Annals of Oncology 2013

Randomized trial of autologous cellular immunotherapy with Sipuleucel-T in androgen dependent prostate cancer. Clinical Cancer Research 2011

Open-label, multicenter study of sipuleucel-T in men with metastatic castrate-resistant prostate cancer (mCRPC) previously treated with sipuleucel-T: Evaluation of antigen presenting cell (APC) activation and ELISPOT data. Journal of Clinical Oncology 2013

Randomized, Double-Blind, Phase III Trial of Ipilimumab Versus Placebo in Asymptomatic or Minimally Symptomatic Patients With Metastatic Chemotherapy-Naive Castration-Resistant Prostate Cancer. Journal of Clinical Oncology 2017

Early evidence of anti-PD-1 activity in enzalutamide-resistant prostate cancer. Oncotarget

All immunotherapy papers
Cytokine-mediated mechanisms of adaptation to chemotherapy in prostate cancer Cell intrinsic and extrinsic induction of cytokine expression and activity represents important candidate mechanisms of acquired chemotherapy resistance. Using pre- and post-treatment patient specimens and laboratory-based models, we reported a role in human tumor treatment resistance for Monoamine Oxidase A, WNT16B, CCL2, and GDF15. Monoamine Oxidase A and CCL2 are suitable for therapeutic targeting. WNT16B is a first report of an adaptive response in tumor stroma that in turn, through paracrine mechanisms, regulates tumor cell resistance.

Chemotherapy-induced monoamine oxidase expression in prostate carcinoma functions as a cytoprotective resistance enzyme and associates with clinical outcomes. PLoS One 2014

Treatment-induced damage to the tumor microenvironment promotes prostate cancer therapy resistance through WNT16B. Nature Medicine 2012

CCL2 is induced by chemotherapy and protects prostate cancer cells from docetaxel-induced cytotoxicity. The Prostate 2010

Prostate Cancer-Associated Gene Expression Alterations Determined from Needle Biopsies. Clinical Cancer Research 2009

All papers on cytokine mediated resistance: COMING SOON
Development of strategies to target vitamin D receptor signaling for cancer therapy. To harness the growth inhibitory activity of the vitamin D receptor ligands while limiting hypercalcemia, we developed an intermittent, high-dose calcitriol dosing strategy from an investigator-initiated phase I study through initial and expanded phase II studies and on to a national phase III clinical trial. The phase III effort did not demonstrate an improvement in overall survival, however this work was a rare example of an investigator-led drug repurposing strategy that attracted substantial capital and moved through to phase III development. The strategy remains the best way to deliver potent vitamin D receptor stimulation for therapeutic purposes that may be exploited in other clinical settings including cancer and hyperproliferative conditions.

A Phase I Trial of Pulse Calcitriol in Patients with Refractory Malignancies: Pulse Dosing Permits Substantial Dose Escalation. Cancer 2001

Weekly High-Dose Calcitriol and Docetaxel in Metastatic Androgen-Independent Prostate Cancer. Journal of Clinical Oncology 2003

Phase I study of Weekly DN-101, a New Formulation of Calcitriol, in Patients with Cancer. Cancer Chemotherapy and Pharmacology 2007

Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. Journal of Clinical Oncology 2007

All papers on vitamin D