Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Hormone Therapy Response Associated with Signaling Activity in Circulating Cancer Cells

By BiotechDaily International staff writers
Posted on 07 Nov 2012
A study monitoring hormone receptor activity in tumor cells from patients being treated for resistant metastatic prostate cancer has found that such monitoring may be useful for indicating which patients will be more likely to respond well to continued therapy.

Treatments that inhibit the androgen receptor (AR) pathway, androgen-deprivation therapy (ADT), are initially highly effective in most patients with metastatic prostate cancer (MPC); however, since cancer cells often develop resistance, secondary hormonal therapies are being tested to suppress androgen receptor reactivation. There are variable responses to such secondary therapy, but no reliable biomarkers are available to guide the use of AR pathway inhibitors in treating resistant MPC. A collaborative team of researchers led by Prof. Daniel A. Haber, MD, PhD, and director of the Massachusetts General Hospital Cancer Center (Charlestown, MA, USA) have now established a method using microfluidic capture of circulating tumor cells (CTCs) to isolate cancer cells from the blood of patients with MPC and single-cell immunofluorescence analysis to measure androgen receptor signaling activity in the individual CTCs.

Monitoring was performed on CTCs from patients with castration-resistant prostate cancer (CRPC), before and after therapeutic interventions. Prior to the initiation of ADT, the AR pathway was turned on in most CTCs from newly diagnosed patients. Initiation of first-line ADT induced a profound switch from “AR-on” to “AR-off” CTCs. In patients whose cancer had become resistant after initially responding well to androgen-deprivation therapy, the CTCs population became highly variable - some CTCs were AR-on, others AR-off, and still others had characteristics of both AR-on and AR-off. The presence of cells with a mixed AR signaling pattern was associated with an adverse treatment outcome. In addition, in patients treated with a new drug, abiraterone acetate, which achieves more complete androgen deprivation than earlier treatments, an increased percentage of AR-on CTCs despite abiraterone treatment was associated with decreased overall survival.

The assay may provide a valuable marker to help target such treatments to patients more likely to respond to second-line therapies. "This study is a proof of principle that it is possible to monitor, in patients with metastatic prostate cancer, the androgen receptor signaling pathway in real time, repeatedly and noninvasively," said Prof. Haber. He added, "As more drugs are developed that target the different pathways that drive the recurrence of metastatic prostate cancer in different patients, it will become essential to know which drug and which pathway is relevant in each patient. Our assay will be an effective way to interrogate the tumor and follow it during the course of treatment to monitor therapy response and the emergence of drug resistance."

The study was published early online October 23, 2012, in Cancer Discovery, a journal of the American Association for Cancer Research.

Related Links:
Massachusetts General Hospital Cancer Center
American Association for Cancer Research


Channels

Genomics/Proteomics

view channel
Image: Cancer cells, left, were pretreated with a drug that blocks the ERK signal, and right, without the pretreatment. Top cells are untreated, while the bottom ones are stimulated (Photo courtesy of the Weizmann Institute of Science).

Prevention of ERK Nuclear Translocation Blocks Cancer Proliferation in Animal Models

A team of cell biologists has shown that the cancer promoting effects of ERK dysregulation can be blocked by low molecular weight drugs that prevent translocation of this kinase from the cells' cytoplasm... Read more

Drug Discovery

view channel
Image: Star-like glial cells in red surround alpha-beta plaques in the cortex of a mouse with a model of Alzheimer\'s disease (Photo courtesy of Strittmatter laboratory/Yale University).

Experimental Cancer Drug Reverses Symptoms in Mouse Model of Alzheimer's Disease

An experimental, but clinically disappointing drug for treatment of cancer has been found to be extremely effective in reversing the symptoms of Alzheimer's disease (AD) in a mouse model.... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 

Events

21 Apr 2015 - 23 Apr 2015
21 Apr 2015 - 23 Apr 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.