Progress Report: Atish Choudhury, MD, Ph.D

Investigator: Atish Choudhury, MD, PhD – Assistant Professor, Dana-Farber Cancer Institute

Molecular Determinants of Hormone Refractory Prostate Cancer

Metastatic prostate cancer initially responds to androgen deprivation therapy (ADT; blockade of male hormones such as testosterone) resulting in tumor regression and improved clinical performance. This is because prostate cancer cell growth and survival is driven by the activity of androgens. However, with time patients inevitably become resistant to ADT and enter a potentially lethal, castration resistant prostate cancer (CRPC) disease state. Dr. Choudhury’s goal is to identify “druggable” targets that cause androgen resistance with the overarching objective of discovering and developing novel therapeutics that prevent or slow the transition to CRPC.

To accomplish this goal, Dr. Choudhury is investigating a human prostate epithelial cell-line that is genetically modified to express oncogenes (cancer-causing genes). This cell-line will only form prostate tumors in mice that produce testosterone. To identify molecules that support prostate cancer growth in castrate conditions (androgen independent) Dr. Choudhury expressed 354 human kinases (enzymes that regulate cell signaling) in the cell-line, one at a time and transplanted the cells into castrated mice. He found that the expression of 16 different kinases were capable of promoting tumor growth in castrate mice. Analysis of human CRPC tumor specimens revealed that the protein levels of 6 of the kinases were elevated when compared to androgen sensitive prostate tumor specimens.

In his final year as a PCF Young Investigator, Dr. Choudhury will determine which kinases play an essential role in the development of CRPC in patients. This knowledge will advance efforts in developing novel agents to treat advanced, lethal, CRPC.

Terms to know from this article:

androgen

A type of hormone that promotes the development and maintenance of male sex characteristics.

Testosterone

A hormone that promotes the development and maintenance of male sex characteristics.

Regression

A decrease in the size of a tumor or in the extent of cancer in the body.

Tumor

A mass of excess tissue that results from abnormal cell division. Tumors perform no useful body function. They may be benign (not cancerous) or malignant (cancerous).