Category: Laboratory Research

Weill Cornell Breakthrough Research: Shutting Down DLBCL Master Protein; Potential for New Treatments

Reporting in Nature Immunology, Weill Cornell’s Dr. Ari Melnick and his research team have reported an important research breakthrough in diffuse large-B cell lymphoma (DLBCL) that may offer hope for new treatments for aggressive lymphomas.

Dr. Melnick has found that it is possible to shut down the protein Bcl6, a powerful master regulatory transcription factor that is the key to survival for many aggressive lymphomas arising from the B-cells.

“The finding comes as a very welcome surprise,” says the study’s lead investigator, Dr. Ari Melnick, Gebroe Family Professor of Hematology/Oncology and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell.

The protein Bcl6 was previously considered too complex to target with individual drugs, because of its centrality in the functioning of the body’s healthy immune cells.

“This means the drugs we have developed against Bcl6 are more likely to be significantly less toxic and safer for patients with this cancer than we realized,” says Dr. Melnick.

DLBCL is the most common subtype of non-Hodgkin lymphoma — the seventh most frequently diagnosed cancer, with many patients resistant to currently available treatments. Presently, there are ongoing clinical trials for those suffering from non-Hodgkin’s lymphoma and other forms of lymphoma at the Weill Cornell Lymphoma Center.

The full press release can be read here.

Weill Cornell Researchers: Velcade + PD 0332991 Weaken & Defeat Myeloma Cells, Potential for Lymphoma

In laboratory experiments, researchers at Weill Cornell Medical College have demonstrated that the cancer fighting effects of Velcade (bortezomib) and PD 0332991  were exponentially multiplied when used together in their laboratory studies on multiple myeloma tumor cells.

The normal cellular growth cycle is derailed in cancer. Uncontrolled growth and multiplication is often the result. The researchers found that PD 0332991 stops the cellular cycle in a vulnerable moment, leaving the cancer cell wide open for cellular destruction by Velcade.

The study, published online last month by the journal Blood, is the first to show that precise timing of therapies that target a cancer cell’s cycle — the life phases leading to its division and replication — disables key survival genes, resulting in cell death. The drug that delivers the weakening jab at the cell cycle is the experimental agent PD 0332991, which allows Velcade, a proteasome inhibitor already approved for use in myeloma and lymphoma, to land the final defeating blow at lower than normal doses.

Dr. Selina Chen-Kiang, professor of Pathology and Laboratory Medicine and of Microbiology and Immunology at Weill Cornell Medical College was the lead scientist on the study. In an interview Dr. Chen-Kiang said:

“Because robust functioning of the cell cycle is crucial to cancer growth and survival, this mechanism-based strategy could theoretically be used against many kinds of cancers.”

The same combination is being tested in patients with mantle cell lymphoma in a Weill Cornell investigator-initiated study led by Dr. John Leonard. Click here for more information about the mantle cell lymphoma study.

 

Weill Cornell’s Dr. Cerchietti Receives Doris Duke Clinical Scientist Award for Study of B-Cell Lymphoma

Dr. Leandro Cerchietti

Dr. Leandro Cerchietti has received a Doris Duke Clinical Scientist Development Award (one of only 12 such awards given yearly by the Doris Duke Foundation). Funding is $150,000 per year spanning 3 years.

Dr. Cerchietti’s project centers on the role of metabolism in determining the clinical behavior of tumors, using metabolomic profiling for the study of B-cell lymphoma.

“Metabolism” is a term that refers to all the biochemical processes of an organ, tumor, or cell, that sustain life. These processes allow cells to grow, reproduce, maintain their structures and respond to environmental changes. Dr. Cerchietti’s study will reveal how — and what — the lymphoma “eats” to survive. It will also explore how these pathways can be “manipulated” in order to “starve them to death.” The goals is to ultimately launch the development of a new class of specific (and non-toxic drugs), and treatments, that could benefit patients with lymphomas.

“We will harness the power of metabolomic profiling to detect certain biological processes in patients; to ascertain whether drugs are hitting their targets in vivo; and to predict clinical outcomes in patients. I think this work has the potential to make important scientific and translational contributions to the diagnosis and treatment of B-cell lymphomas,” says Dr. Cerchietti.