Noninvasive assay monitored treatment response in patients with metastatic prostate cancer

October 23, 2012

Deciding the ideal treatment for patients with metastatic prostate cancer that stops responding to initial therapy could be guided by certain analyses of cancer cells isolated from the patients' blood, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

"The growth and survival of are very dependent on signals that the cancer cells receive through a protein called the androgen receptor," said Daniel A. Haber, M.D., Ph.D., director of the Massachusetts General Hospital Cancer Center in Boston and project leader of the Stand Up To Cancer and Clinical Applications of Circulating Tumor Cell Chip Dream Team. "Treatments that deprive the androgen receptor of its signals are initially highly effective in most patients with metastatic prostate cancer. Unfortunately, prostate cancer, like all cancers, undergoes evolution during therapy, and this can confer resistance to treatment."

Haber and his colleagues established a way to isolate cancer cells from the blood of patients with prostate cancer and to measure readouts of androgen receptor signaling in each of the individual cancer cells in the blood.

Prior to the initiation of androgen-deprivation therapy, the androgen receptor signaling pathway was turned on in most of the cancer cells in the blood of patients with newly diagnosed metastatic prostate cancer. After the initiation of androgen-deprivation therapy, the pathway turned off in the circulating .

However, in patients whose prostate cancer had progressed after initially responding to androgen-deprivation therapy, the cancer cells in the blood were highly variable. Some cells had the androgen receptor signaling pathway turned on while other cells had it turned off. Yet other cells had characteristics of the signaling pathway being both on and off. The presence of cells with a mixed androgen receptor signaling pattern was associated with an adverse .

In addition, in patients treated with a new drug, abiraterone, which achieves more complete androgen deprivation than earlier treatments, an increased percentage of with androgen receptor signaling turned on despite abiraterone treatment was associated with decreased overall survival.

"This study is a proof of principle that it is possible to monitor, in patients with metastatic prostate cancer, the signaling pathway in real time, repeatedly and noninvasively," Haber said. "Our approach allowed us to monitor whether initial androgen-deprivation therapy was keeping the androgen signaling pathway shut down or whether the tumor was becoming resistant, and if so, by what mechanism."

"As more drugs are developed that target the different pathways that drive the recurrence of metastatic in different patients, it will become essential to know which drug and which pathway is relevant in each patient," he said. "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."

Explore further: Study identifies new prostate cancer drug target

Related Stories

Study identifies new prostate cancer drug target

February 6, 2012
Research led by Wanguo Liu, PhD, Associate Professor of Genetics at LSU Health Sciences Center New Orleans, has identified a new protein critical to the development and growth of prostate cancer. The findings are published ...

Prostate cancer gets around hormone therapy by activating a survival cell signaling pathway

June 14, 2011
Cancer is crafty. When one avenue driving its growth is blocked by drugs targeting that path, the malignancy often creates a detour, finding an alternative route to get around the roadblock.

Recommended for you

Lung cancer triggers pulmonary hypertension

November 17, 2017
Shortness of breath and respiratory distress often increase the suffering of advanced-stage lung cancer patients. These symptoms can be triggered by pulmonary hypertension, as scientists at the Max Planck Institute for Heart ...

Researchers discover an Achilles heel in a lethal leukemia

November 16, 2017
Researchers have discovered how a linkage between two proteins in acute myeloid leukemia enables cancer cells to resist chemotherapy and showed that disrupting the linkage could render the cells vulnerable to treatment. St. ...

Computer program finds new uses for old drugs

November 16, 2017
Researchers at the Case Comprehensive Cancer Center at Case Western Reserve University School of Medicine have developed a computer program to find new indications for old drugs. The computer program, called DrugPredict, ...

Pharmacoscopy improves therapy for relapsed blood cancer in a first clinical trial

November 16, 2017
Researchers at CeMM and the Medical University of Vienna presented a preliminary report in The Lancet Hematology on the clinical impact of an integrated ex vivo approach called pharmacoscopy. The procedures measure single-cell ...

Wider sampling of tumor tissues may guide drug choice, improve outcomes

November 15, 2017
A new study focused on describing genetic variations within a primary tumor, differences between the primary and a metastatic branch of that tumor, and additional diversity found in tumor DNA in the blood stream could help ...

A new strategy for prevention of liver cancer development

November 14, 2017
Primary liver cancer is now the second leading cause of cancer-related death worldwide, and its incidences and mortality are increasing rapidly in the United Stated. In late stages of the malignancy, there are no effective ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.