AACR-Novocure Career Development Award for Tumor Treating Fields Research
The AACR-Novocure Career Development Award for Tumor Treating Fields Research represents a joint effort to promote and support early-career investigators who are conducting innovative research focused on Tumor Treating Fields. These grants are intended to provide a deeper understanding of the mechanisms of action of this anti-cancer treatment modality and to accelerate the development of new treatment strategies to advance therapeutic options for cancer.
Tumor treating fields (TTFields) cause replication stress and inhibit the DNA damage repair process due to decreased expression of genes involved in the Fanconi anemia pathway and cell cycle checkpoint. However, the exact cause of the downregulation of these genes has been elusive. Preliminary quantitative proteomics data point to a putative involvement of the CDK–Rb–E2F axis in treatment response to TTFields. Dr. Karanam is set to explore TTFields-induced proteome and metabolome changes in in vitro and in vivo lung and pancreatic cancer models, and to determine the therapeutic potential of combining E2F and CDK4/6 inhibitors with TTFields.
Dr. Karanam received his PhD in cancer biology at the University of Greifswald, Germany. He pursued postdoctoral training at George Washington University. He is currently an instructor at UT Southwestern Medical Center, where his research includes the interrogation of TTFields mechanisms of action.
Acknowledgment of Support
I am deeply honored to receive the AACR-Novocure Career Development Award for Tumor Treating Fields Research. This award affords me the opportunity to understand the system level effects of TTFields exposure through trans-omics approaches in order to find novel combination therapies that can be translated into tangible benefits for cancer patients.
Mitotic disruption induced by TTFields leads to immunogenic cell death, causing an influx of T cells into tumors. This suggests a potential synergy between TTFields and immunotherapeutic approaches such as checkpoint blockade and personalized cancer vaccines. Dr. Rubinsteyn is set to assess TTField-induced neoantigen formation and the impact of the anti-PD-1 (or anti-PD-L1)/TTField combination on tumor infiltrating T cells. In pursuit of these aims, he plans to interrogate the genomic landscape of TTFields-induced mutations and the functionality of neoantigen specific T cells.
Dr. Rubinsteyn received his PhD in computer science from NYU. After graduate school, he pursued computational cancer immunotherapy research at the Icahn School of Medicine at Mount Sinai. He subsequently helped initiate and conduct three personalized cancer vaccine trials at Mount Sinai. Currently, he is an assistant professor in the Department of Genetics at UNC, as well as a member of the Computational Medicine Program and the Lineberger Cancer Center.
Acknowledgement of Support
I collaborate extensively with Dr. Adilia Hormigo on her vaccine trial for glioblastoma in combination with TTFields. This AACR-Novocure Career Development Award allows me to delve deeper into the biology underlying this therapeutic combination. As we better understand the ways in which TTFields augments the anti-tumor immune response, we will be able to design more effective immunotherapeutic combinations.