Weill Cornell Researchers Create Device to Collect Living Prostate Tumor Cells; Potential to Inform Development of New Drugs

Cancer metastases (spreading from the initial cancer tumor to other parts of the body) account for the majority of cancer-related deaths because of poor responses to anti-cancer therapies.

Researchers at Weill Cornell Medical College, in collaboration with engineers from Cornell University in Ithaca, NY, have created a new device that searches the blood for living, circulating tumor cells. The device allows researchers to capture and molecularly characterize circulating tumor cells (CTCs) isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. This new device will allow physicians to monitor drug response at the cellular level, which will potentially allow physicians to tailor prostate cancer treatments to an individual patient. The device is the first functional assay of a microtubule-targeting agent on living circulating tumor cells microfluidically extracted from patient blood.

The researchers  include Dr. Brian Kirby at Cornell University and  Dr. Paraskevi Giannakakou, Dr. Neil Bender, Dr. Scott Tagawa and Dr. David Nanus at Weill Cornell Medical College.

Background

Circulating tumor cells are prostate cancer cells which have escaped from prostate tumors (from the prostate, bone, or other areas) and are circulating in blood.  The FDA has cleared a specific type of test to enumerate (or count) the number of these cells in a tube of blood, called the CellSearch test.  The advantage of this test is that it has been well studied at many centers and has been validated to yield prognostic information.  However, this test is not very sensitive; men with metastatic prostate cancer may have no detectable cells.  In addition, this test is not specific to prostate cancer – the same test also picks up different cells (it is also cleared for breast and colon cancer).

The New Device

The collaborating researchers at Weill Cornell and Cornell University developed a new test called the “Geometrically Enhanced Differential Immunocapture” device. The device has been optimized based upon flow and size characteristics of prostate cancer cells.  Importantly, the device uses additional technology developed at Weill Cornell, a monoclonal antibody against Prostate Specific Membrane Antigen (PSMA).  The anti-PSMA antibody called J591, developed by Dr. Neil Bander in the Weill Cornell Department of Urology,  specifically recognizes the PSMA protein which is present on the surface of virtually all prostate cancer cells.  The combined technology has allowed Weill Cornell researchers to collect and analyze more prostate cancer cells than the standard device.

In addition to prognostic information, it is hoped that the capture and analysis of CTCs may serve as a type of “liquid biopsy” to allow researchers to gain information about a patient’s tumor.  Initial work has led to promising results in the ability to predict future responses to chemotherapy based upon a blood test prior to the drug or after only 1 dose.

The authors write, “these measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents.”

Click here to read the published research paper.

Scientists Discover New Prostate Cancer Subtype

Researchers at Weill Cornell Medical College, collaborating with researchers at the Broad Institute of MIT and Harvard and the Dana-Farber Cancer Institute, have uncovered a distinct molecular subtype of prostate cancer, which is prevalent among 15% of men with the disease.

In the study, published online May 20 in the journal Nature Genetics, investigators describe how they discovered novel mutations in the SPOP (“S-pop”) gene in numerous patient tumors, saying this alteration is thus far unique to prostate cancer and represents a distinct molecular class that might assist in cancer diagnosis and treatment. Researchers suspect the mutations alter the way cells tag proteins for degradation, leading to an accumulation of dangerous molecules that drive the growth of cancer, perhaps from the beginning.

This type of mutation is unique to prostate cancer. By targeting the mutations in the SPOP gene, a new class of cancer diagnosis and treatment can be developed.

This finding adds to a string of discovery of other genes linked to prostate cancer over the years by this team of investigators, the totality of which is painting a comprehensive picture of how genetic alterations contribute to prostate cancer — the most common cancer in men aside from skin cancer, accounting for the second leading cause of cancer deaths.

Click here to read the published research paper.

Weill Cornell Investigators Among Grant Recipients to Study Metastatic Prostate Cancer

An international team of investigators from centers in the United States and the United Kingdom, including Weill Cornell Medical College, have been awarded a grant for $10 million over a three-year period to study the molecular underpinnings of metastatic prostate cancer while creating a comprehensive testing system to optimize personalized treatments.

Stand Up To Cancer (SU2C) and the Prostate Cancer Foundation (PCF), along with the American Association for Cancer Researc, SU2C’s scientific partner, announced the formation of a new “Dream Team” dedicated to prostate cancer research.

Weill Cornell Medical College investigators include Dr. Mark Rubin, the project’s principal investigator at Weill Cornell, and Dr. Himisha Beltran.

One of the project’s goals is to try to understand why therapies can become ineffective, despite working initially, and if patients may be treated with other types of therapies or participate in clinical trials. The researchers plan to develop cell line models to study tumor mutations to determine, for example, if they are the culprit behind such cancer recurrences in patients. In addition, the investigators plan to study novel combinations of drugs in clinical trials, including exploring the use of PARP inhibitors and drugs that inhibit the PTEN pathway, which is involved in cell signaling and growth. PTEN is a well known tumor suppressor gene. PARP inhibitors prevent an enzyme involved in DNA repair, especially in the repair of tumor cells, from working.

Click here to read more about the grant.