Featured LRF Researcher – Dr. Selina Chen-Kiang, PhD
Dr. Selina Chen-Kiang has been Professor of Pathology and Professor of Immunology and Microbial Pathogenesis at the Weill-Cornell Medical College since 1996. After receiving her PhD in Genetics and Development at Columbia University she went on to become a Jane Coffin Child Cancer Fellow and completed her postdoctoral training in molecular biology at Rockefeller University. She is also a recipient of a Lymphoma Research Foundation (LRF) Mantle Cell Lymphoma (MCL) Planning Grant and MCL Correlative Grant.
With a research focus centered on studying cell cycle control of cancer and B-cell immunity, Dr. Chen-Kiang's interest in lymphoma is driven by the rapid advent of novel agents in recent years and the potential to improve treatment outcome by innovative approaches. "We are now able to bring discoveries from 'bench to bedside' in real-time, learning from clinical findings at the bedside, and bringing these findings back to the bench to learn some more." That said, despite the rapid pace of therapy development, she agrees that "there are still lymphomas that are incurable, such as mantle cell lymphoma". Because loss of cell cycle control is a hallmark of MCL, her background and knowledge could make a genuine difference.
As a recipient of an LRF Mantle Cell Lymphoma Planning Grant and MCL Correlative Grant, Dr. Chen-Kiang acknowledges that the LRF support has been instrumental in the success of her research in lymphoma thus far; "it gave me a head-start before we even published the first paper on mantle cell lymphoma." With the MCL Correlative Grant, she was able to complete the proposed study of targeting the cell cycle in MCL using a selective CDK4/CDK6 inhibitor. She further developed a novel combination therapy that both inhibits tumor cell division and renders the cells susceptible to killing by a partner agent, using the selective CDK4/CDK6 inhibitor.
The innovative aspect of her work lies in understanding the molecular mechanism that renders tumor cells susceptible to drug killing through manipulating the cell cycle and examining specific patient responses at the genetic and molecular levels. This means that "we can now identify the gene expression signature that differentiates patients who respond or do not respond to a specific CDK4/CDK6-based combination therapy, and find out which therapy will suit them best. We already have four different combinations as of today. After this we hope to tailor treatments for each patient, allowing us to choose the one that is most promising." The contribution of the LRF grant is evident in the extensive progress that Dr. Chen-Kiang and her team have made towards matching MCL patients with specific combination therapies. One such drug, Bruton's tyrosine kinase (BTK) inhibitor, has been reported to have a success rate of ~65% in MCL patients as a single agent, but the basis for resistance to this drug in the remaining ~30% of MCL patients is still unknown. She explains that "we are able to put this very promising drug together with the CDK4/CDK6 inhibitor, and further enhance the activity of the BTK inhibitor". Dr. Chen-Kiang also points to the exciting PIK3ß inhibitor, which is effective in chronic lymphocytic leukemia (CLL), and indolent lymphoma, but not in non-indolent lymphoma such as MCL. By manipulating the cell cycle, we have been able to make MCL cells sensitive to the PIK3ß inhibitor.
Dr. Chen-Kiang's current work in this area, "attacking the disease by manipulating the cell cycle" adds to the exciting developments within lymphoma research. "We are now able to combine targeting the cell cycle with a selective reagent, killing the tumor cells using a second specific agent. This leads to a deeper understanding of the underlying mechanism, which in turn allows us to characterize which genes are producing different responses."
Today, Dr. Chen-Kiang feels very fortunate to be able to make a contribution toward treating lymphoma and finds it very gratifying to be able to "apply fundamental findings in real time, designing new therapies and putting them into practice right away, to benefit the patients." As treatments continue to develop, "researchers are able to refine their hypothesis and follow the patients' response at the genetic level. This then allows researchers to identify biomarkers for treatment stratification. I feel very privileged to be doing this. How many people can do what they are passionate about and make a difference in treating patients?" Dr. Chen-Kiang also acknowledges that she is "very fortunate to be located in an institution where the interactions between basic scientists and physicians are seamless."
When advising newly diagnosed lymphoma patients and their families, Dr. Chen-Kiang urges them "not to despair", adding that "this is a very exciting time; a lot of people have dedicated themselves to finding a better therapy and a cure." Those affected by lymphoma can take heart from the fact that; "clinicians and scientists continue to work together, the significance of this means that we are seeing definitive results and treatments that are constantly improving."
To learn more about the LRF research program, or the research and investigators supported by the Foundation please click here.
To read about other Featured LRF Researchers, click here.