KDM5 as a Biomarker of Docetaxel Resistance in Prostate Cancer

Project Overview

• Androgen deprivation therapy (ADT) has been the mainstay of treatment for metastatic hormone sensitive prostate cancer (mHSPC). However, chemotherapy, primarily with docetaxel, has been reserved for metastatic castration-resistant prostate cancer (mCRPC), a type of androgen independent prostate cancer.
• Currently there is a need to identify a strategy of patient stratification, sparing patients from the long-term side effects of ADT without losing efficacy. 
• Dana-Farber scientists have created a method for diagnosing prostate cancer patients according to KDM5 protein expression to help guide appropriate treatment selection.
• This platform technology is available for licensing.

Technology

Most prostate cancer is initially androgen dependent, and androgen deprivation therapy (ADT) through either surgery or medical treatment rapidly leads to apoptosis of androgen-dependent cancer cells. Therefore, ADT has been the mainstay of treatment for metastatic hormone sensitive prostate cancer (mHSPC) for more than 70 years. 

In many cases, however, some cancer cells survive and become androgen independent or unresponsive, leading to recurrence of prostate cancer. Chemotherapy has been reserved for metastatic castration-resistant prostate cancer (mCRPC), a type of androgen independent prostate cancer. Taxanes and DNA damaging agents are two major classes of chemotherapeutics used for treating prostate cancer. Among these drugs, the taxane docetaxel, is currently a first-line therapy for mCRPC. 

Scientists at Dana-Farber have developed a technology for screening and diagnosing prostate cancer, as well as for selecting the proper therapeutic treatment. The technology is based on using KDM5 protein expression levels to identify which patients with hormone-sensitive prostate cancer could benefit from primary castration and taxanes, and which patients with castration-resistant prostate cancer could benefit from docetaxel combined with androgen receptor antagonists.

The method consists in measuring the expression levels of KDM5D in a sample extracted from the patient, and then comparing the measured expression of KDM5D in the sample to a reference expression level of KDM5D in a control sample. 

Team Members: Christopher Sweeney, MBBS, Philip Kantoff, MD, PhD, Kazumasa Komura, MD, PhD, Gwo-Shu Mary Lee, PhD

Applications

• Screening and diagnosis of prostate cancer. 
• Help identify which patients would benefit from the treatment strategy of immediate androgen deprivation therapy plus docetaxel. 
• Identification of a mechanism underlying the clinical benefit, and development of a strategy of patient stratification, sparing some patients of the long-term side effects of ADT without losing efficacy. 

Opportunities

Dana-Farber is looking for the right partner with an interest in licensing these assets for further development. 

Team Members