Tag: castrate-resistant prostate cancer

Dr. Scott Tagawa Presents at American Cancer Research Meeting

Dr. Tagawa
Dr. Tagawa

Weill Cornell’s Dr. Scott Tagawa presented four research posters at this year’s American Association for Cancer Research (AACR) annual meeting. Each of the presentations is summarized below. Click on the title to view the published abstracts.

 

Non-invasive measurement of prostate-specific membrane antigen (PSMA) expression with radiolabeled J591 imaging: a promising biomarker for PSMA-based radioimmunotherapy

J591 is a man-made monoclonal antibody that is able to recognize a protein antigen (PSMA) expressed on virtually all prostate cancer cells, and more so in men with treatment-resistant metastatic disease. When a tiny tag of radioactive material is attached to the J591 antibody, that specifically targets prostate cancer cells, and delivered systemically this is known as radioimmunotherapy. Dr. Tagawa has been conducting clinical trials of the precision radioimmunotherapeutic J591 to determine its ability to eradicate prostate cancer cells that have metastasized. In this poster presentation, Tagawa and colleagues performed a combined analysis of four clinical studies of this radioimmunotherapeutic that examined 130 patients with metastatic treatment-resistant prostate cancer. They found that the levels of PSMA expression—as determined by a non-invasive scan–can be used to indicate response to their radioimmunotherapy.

ERG induces taxane resistance in castration-resistant prostate cancer

Taxanes are a type of chemotherapy drug that are used to treat advanced prostate cancer; however, inevitably prostate cancer patients develop resistance to these chemotherapy drugs. In this poster, Tagawa et al demonstrate that a genetic abnormality (ERG positivity) found in half of all men with prostate cancer plays an active role in inducing resistance to taxane-based chemotherapeutics. Additionally they’ve determined that men with ERG positive tumors have upregulation of another protein (clusterin) that can cause resistance to taxane chemotherapeutics. This work dovetails nicely with Dr. Zoubeidi’s work (see above) and shows the potential to use a drug now in clinical trials (OGX-011) to enhance response to chemotherapy in men whose prostate cancer is positive for the ERG genetic aberration.

Using CTCs to interrogate mechanisms of taxane resistance in the prospective TAXYNERGY clinical trial in prostate cancer

This poster describes a prospective, randomized multi-site clinical trial that will enroll 100 men with treatment resistant prostate cancer and use advanced technology to capture and analyze cancer cells that are freely circulating in their bloodstreams. This trial will allow the researchers to look for early signs of treatment response or failure in individual cancer cells and examine the genetic and other molecular factors that indicate or lead to either a response or lack of response to chemotherapy. This is one of the few studies to utilize blood-based biomarkers in a prospective fashion. It is also a demonstration of cooperation between academic partners and the pharmaceutical industry—one that was facilitated by the Prostate Cancer Foundation.

Prostate circulating tumor cells metastasize to bone via E-selectin expressed on endothelia cells

This poster describes a molecular dance that prostate tumor cells exploit as they metastasize to bone. Understanding and characterizing the mechanisms that tumor cells use exit the bloodstream and to home to bone and set up shop should allow researchers to develop ways to interrupt the process and prevent circulating prostate cancer tumor cells from setting up cancerous shop in men’s bones.

Cornell Researchers Discuss Device to Collect Living Prostate Tumor Cells: Video

On June 12, 2012, Cornell researchers David Nanus, Brian Kirby and Paraskevi Giannakakou discussed their new microfluidic device that collects circulating, living prostate cancer tumor cells from blood.

The research, conducted collaboratively between Cornell University and Weill Cornell Medical College, aims toward tailoring cancer treatment and improving patient survival. Click below to view the presentation.

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.

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