Tag: New York Presbyterian

Weill Cornell Research: ALK Inhibitors Completely Eradicate DLBCL with ALK Translocation in Laboratory Animals

In a significant finding recently published in PLoS One, researchers at Weill Cornell Medical Center showed that ALK inhibitors (drugs that act on tumors with the protein ALK) could completely eradicate Diffuse Large B-Cell Lymphoma (DLBCL) with ALK mutation in laboratory animals. This is an important finding considering that patients with DLBCL with ALK mutations are resistant to common chemotherapy treatments.

Patients diagnosed with ALK positive DLBCL may, therefore, be candidates for therapeutic trials of ALK inhibitors. The incorporation of ALK status determination into the diagnosis of DLBCL could help identify these patients more readily. There are several ALK inhibitors under clinical testing for ALK positive tumors.

Background

BCL6 is the most frequent oncogene (a gene that has the ability to cause cancer) in Diffuse Large B-Cell Lymphoma (DLBCL). However in a proportion of DLBCL other genes play a leading role in the oncogenic process. In an effort to personalize the treatment for patients with DLBCL, we found that a protein called ALK plays an oncogenic role in a subset of DLBCL.

We established and characterized the first ALK positive DLBCL line with a mutation that causes ALK to be expressed and active at very high levels, causing tumor cells to proliferate (reproduce rapidly). This cell line was obtained from the bone marrow tissue of a patient diagnosed with DLBCL. We developed pre-clinical animal models of DLBCL with ALK mutation, and we treated them with specific ALK inhibitors. As described above, the research showed that ALK inhibitors could completely eradicate DLBCL with ALK mutation in animals.

Click here to read the published research paper.

Clinical Trial: Bruton’s Tyrosine Kinase (Btk) Inhibitor PCI-32765 in Relapsed/Refractory Mantle Cell Lymphoma

Update: this study is closed to enrollment. 

Bruton tyrosine kinase (Btk) is an enzyme that plays a crucial role in the development of the normal immune system. Recent studies indicate that Btk may also play a role in many B-cell lymphomas.

PCI-32765 is an investigational drug that irreversibly inhibits Btk. A phase 1 trials performed at several sites, including Weill Cornell Medical Center, demonstrated that PCI-32765 was well tolerated with minimal side effects.

In this phase 2 study, we are evaluating the efficacy of PCI-32765 (four pills take once daily) in patients with previously treated mantle cell lymphoma. We hope to learn how well PCI-32765 works and more about its side-effect profile.

To learn more about this study, please contact June Greenberg, RN at (212) 746-2651 or email June at jdg2002@med.cornell.edu.

Click here to view the clinical and research profile of Peter Martin, MD, the physician leading the study at Weill Cornell Medical Center.

Weill Cornell Investigational Drug Shuts Down Aggressive Form Of Leukemia That Affects Children

In a significant breakthrough published recently in Nature, researchers at Weill Cornell Medical College and the University of California, San Francisco, have been able to overcome resistance of a form of leukemia to targeted therapy, demonstrating complete eradication of the cancer in cell and animal studies.

The study shows that an investigational drug, RI-BPI, developed at Weill Cornell, in combination with the drug Gleevec shut down stem cells responsi ble for about one-third of acute lymphoblastic leukemia (ALL), a cancer of white blood cells that affects young children as well as older adults. This form of ALL has the so-called Philadelphia chromosome, which is also found in chronic myelogenous leukemia (CML). But while Gleevec has greatly improved survival in CML, it has had a less dramatic effect in ALL, and most patients still die within a relatively short time frame.

That prognosis may change given these results, says co-senior investigator Dr. Ari Melnick, associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College, and a hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. Dr. Melnick and his colleagues developed RI-BPI, and they have shown its potent effects in non-Hodgkin’s lymphoma (NHL) with no toxicity to normal cells. The drug targets the transcription factor BCL6, a master regulator of hundreds of genes that provides strong growth signals to NHL cells.

“I am surprised, and extremely glad, to see that RI-BPI has such strong activity in a leukemia. This opens up the possibility that the agent will have similar beneficial effects in other tumor types,” says Dr. Melnick.

Click here to read the press article describing the study results. Click here to read the published research paper.

Background on the development of RI-BPI at Weill Cornell Medical Center: Diffuse Large B ell lymphoma (DLBCL) is a common and aggressive subtype of lymphoma that is frequently associated with deregulation of the oncogene BCL6 (oncogene is a genetic material that carries the ability to induce cancer). Deregulated BCL6 activity keeps B cells in a rapidly proliferating (reproducing) state. The high levels of BCL6 expression in DLBCL coupled with the low or nil expression of BCL6 in normal cells have made BCL6 an attractive candidate for anti-cancer drug development.

Personalized lymphoma medicine offers the hope that by identifying lymphoma-causing mutations in critical regulatory genes, we can target these mutant proteins to cure lymphoma while limiting the side effects. Continue reading “Weill Cornell Investigational Drug Shuts Down Aggressive Form Of Leukemia That Affects Children”