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Q&A With Ari Melnick, MD Bookmark and Share

With the recent publication of his team's study, A Small-Molecule Inhibitor of BCL6 Kills DLBCL Cells In Vitro and In Vivo, in Cancer Cell, Ari Melnick, MD, Associate Professor at Weill Cornell Medical College answers some questions for LRF on why this study is important for patients and what it could mean for the future of lymphoma research. Dr. Melnick currently sits on LRF's Scientific Advisory Board and is a 2009 follicular lymphoma grant recipient.

How did you react when you first learned that your research discovered the inhibitor 79-6, attached to BCL6 exactly where hypothesized while blocking BCL6 complex formation within DLBCL cells?
It was awesome to behold. Aside from incredibly exciting, it was rewarding to see that all of the years of effort and scientific research were paying off in way that could be meaningful for patients with lymphoma. When we began this line of research we had had more basic science goals and we did not imagine that it would lead to a potential therapy so quickly. Moreover, it was standard knowledge at the time that it was "impossible" to design small molecule drugs that could do this. We thought that with using state-of-the-art scientific methods and a comprehensive understanding of how BCL6 works, we might be able to develop a BCL6 drug in spite of these reservations, and so it was amazing to see the research come to fruition.

Looking back on previous doubts that this research could lead to promising results, how do you feel about what you and your team have accomplished?
It is a privilege to have the opportunity to do this kind of work; in addition to being scientifically fascinating, it could bring about significant medical advances. My goal in research has always been to study a biological mechanism in great depth in order to achieve the greatest precision and accuracy of understanding of how things work with the hope that someday the information could be harnessed for the purpose of improving bio-medicine. The work has succeeded thanks to the group effort of an international, multi-disciplinary, scientific team, underlining the importance of openness and collaboration in accelerating the pace of scientific discovery.

What do your results mean for DLBCL patients?
BCL6 is the most commonly involved oncogene in DLBCL and a majority of DLBCL tumors appear to be biologically dependent on BCL6. Based on our laboratory work, it seems that DLBCL cells are extremely responsive to BCL6 inhibitors and BCL6 inhibitors do not seem to induce significant toxicity in animals. Our hope is that BCL6 targeted therapy could improve the efficacy of anti-lymphoma therapy and potentially reduce the need for chemotherapy drugs.

How do you foresee DLBCL treatment changing with this new development?
If the drug works as hypothesized based on pre-clinical results, in the future it will be possible to reduce or eliminate chemotherapy drugs from the standard treatment for DLBCL, and in their place use combinations of targeted agents that directly block the molecular mechanisms of disease.

What should current DLBCL patients ask their physicians with regards to this study?
The drugs will not be in clinical trials for several years.

Can you see the results of this study relaying to developments in other lymphoma sub-types in the future?
In addition to DLBCL, it is likely that follicular lymphomas, Burkitt lymphomas and AIDS-related lymphomas could benefit from BCL6 targeted therapy.

Do you have anything else to add?
It is important to underline that lymphoma patients and their families have played the central role in making this science possible through their support of key foundations such as the Lymphoma Research Foundation. In an age where the government has slashed scientific research and reduced the budget of the National Institutes of Health, the best hope to ensure that medical research moves ahead is for all of us to further strengthen foundations like LRF.