A Possible Cause of Resistance to Antiandrogen Treatment for Advanced Prostate Cancer Identified

Analysis of androgen receptor patterns also uncovers a new therapeutic target for advanced disease

A team of researchers in the USA and China led by Dr. Dean Tang at New York State’s Roswell Park Comprehensive Cancer Center has examined androgen receptor (AR) expression patterns in 89 patients with castration-resistant prostate cancer.  Dr. Tang’s team has linked the development of castration-resistant prostate cancer and treatment resistance to a lack of androgen receptor (AR) expression in prostate cancer cells.

The team has also identified a new therapeutic target for advanced prostate cancer. Results of their study appeared September 6 in the journal Nature Communications.

Further research confirmed that cells lacking AR did not respond to treatment with enzalutamide (brand name Xtandi). The researchers report new evidence that combination treatment with enzalutamide  and ABT-199 (brand name Venetoclax), a newly FDA-approved BCL-2 inhibitor, markedly inhibits experimental castrate-resistant prostate cancer. Roswell Park’s Dr. Dean Tang has initiated a phase Ib/II clinical trial based on these findings.

The new findings identify 3 distinct patterns of androgen receptor (AR) expression. AR, a key driver of prostate cancer, is a protein that binds to male hormones. As a way to overcome treatment resistance, the team investigated targeting the protein BCL-2.

Dr. Dean Tang
Dean Tang, MD PhD, Roswell Park researcher.

Continue reading “A Possible Cause of Resistance to Antiandrogen Treatment for Advanced Prostate Cancer Identified”

Genomic Landscape of Metastatic Prostate Cancer Unveiled in New Study

Analysis of Prostate Tumors Reveals Clues to Cancer’s Aggressiveness
Sequencing finds genetic errors common in metastatic tumors

PSA Rising August 4 2018. A comprehensive genetic analysis of metastatic prostate cancer has, for the first time, revealed a number of major ways in which abnormal alterations of the genome propel this aggressive form of the disease.

Using genetic sequencing, scientists revealed the complete DNA makeup of more than 100 aggressive prostate tumors, pinpointing important genetic errors these deadly tumors have in common. The multicenter study lays the foundation for finding new ways to treat prostate cancer, particularly for the most aggressive forms of the disease.

Genomic hallmarks of metastatic prostate cancer
Genomic Hallmarks and Structural Variation in Metastatic Prostate Cancer. Graphical Abstract, source: Cell

Continue reading “Genomic Landscape of Metastatic Prostate Cancer Unveiled in New Study”

An ‘Achilles Heel’ for Aggressive Prostate Cancer Found, UCSF says

Resistant Cancers Self-Destruct When Exposed to Experimental Drug

May 3, 2018. PSA Rising / UCSF / San Francisco researchers have discovered a promising new line of attack against lethal, treatment-resistant prostate cancer. Analysis of hundreds of human prostate tumors revealed that the most aggressive cancers depend on a built-in cellular stress response to put a brake on their own hot-wired physiology. Experiments in mice and with human cells showed that blocking this stress response with an experimental drug — previously shown to enhance cognition and restore memory after brain damage in rodents — causes treatment-resistant cancer cells to self-destruct while leaving normal cells unaffected.

Metastatic prostate cancer cells treated with experimental drug ISRIB.
Metastatic human prostate cancer cells transplanted into a mouse self-destruct (red) when treated with ISRIB, an experimental drug that exposes cancer cells to their full, unhealthy appetite for protein synthesis. Credit: Ruggero Lab / UCSF

The new study was published online May 2, 2018 in Science Translational Medicine. Continue reading “An ‘Achilles Heel’ for Aggressive Prostate Cancer Found, UCSF says”

Taking Prostate Cancer Drug Abiraterone acetate (Zytiga) After a Meal Boosts Impact, Lowers Cost

Monday, 9 April 2018. By taking a high-cost drug with a low-fat meal—instead of on an empty stomach, as prescribed—prostate cancer patients could decrease their daily dose, prevent digestive issues and cut costs by 75 percent, according to a new study in the March 28, 2018, issue of the Journal of Clinical Oncology (JCO).

Abiraterone acetate, marketed as Zytiga®, is a standard medicine prescribed for metastatic castration-resistant prostate cancer. The pharmaceutical company tells patients on Zytiga to take four of the 250 milligram pills first thing in the morning. Then, having gone without food overnight, they must wait at least one more hour before eating breakfast.

“This schedule is not only inconvenient for patients, it’s also wasteful, in several ways,” said the study’s lead author, Russell Szmulewitz, MD, associate professor of medicine at the University of Chicago and a prostate cancer specialist.

Continue reading “Taking Prostate Cancer Drug Abiraterone acetate (Zytiga) After a Meal Boosts Impact, Lowers Cost”