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.
Glioblastoma is the most common primary malignant brain tumor in adults and has a dismal prognosis despite an aggressive treatment regimen. Tumor Treating Fields (TTFields) are a novel noninvasive treatment modality utilizing alternating electric fields demonstrating an increase in overall survival. More research is needed to fully understand the mechanism, timing, and sequence of TTFields-induced effects to further improve its efficacy. Dr. Borst’s group plans to conduct advanced time lapse experiments and use clinically relevant animal models to establish the impact of TTFields on cell cycle duration/ transitions, cell morphology, and cell death.
Dr. Borst obtained his MD at the University of Antwerp and his PhD at the University of Amsterdam. He completed his clinical training in the Department of Radiation Oncology at the Netherlands Cancer Institute. After additional training at the Hokkaido University, Japan, the Institute of Cancer Research, U.K., the Princess Margaret Cancer Centre, Canada, and the University of California, San Francisco, Dr. Borst developed his translational research group investigating novel insights in the treatment response of brain tumors. He now holds a clinical-academic position at the University of Manchester and The Christie NHS Foundation Trust.
Acknowledgment of Support
The AACR-Novocure Career Development Award will enable the setup of advanced research elucidating insights for further knowledge and improvement of efficacy of TTFields treatment. This work will subsequently lead to novel translational studies that are needed to improve the treatment outcome of patients with brain tumors.
Tumor Treating Fields (TTFields) are thought to exhibit primarily anti-mitotic effects on cancer cells. However, recent data supports an emerging role of TTFIelds in modulating cancer cell-extracellular matrix (ECM) phenotypic biophysics. Using primary and metastatic brain tumor 3D culture systems, live-cell microscopy imaging, and data-derived mechanistic computational modeling, Dr. Weis aims to 1) characterize the biophysical response to TTFields, 2) determine the effects of TTFields on the ECM structural architecture and mechanical stiffness, and 3) identify stromal influences that potentiate response to TTFields.
Dr. Weis received his BS in biomedical engineering from Washington University in St. Louis and his MS and PhD in biomedical engineering from Vanderbilt University. He was a postdoctoral fellow at the Vanderbilt University Institute of Imaging Science and a research assistant professor of biomedical engineering at Vanderbilt University prior to joining Wake Forest. He is currently an assistant professor of biomedical engineering at Wake Forest School of Medicine. His research group seeks to develop novel analysis approaches in cancer – combining mechanistic computational modeling with non-invasive imaging data to explore the response to cancer therapy.
Acknowledgment of Support
I am honored to receive this AACR-Novocure Career Development Award for Tumor Treating Fields Research. This award will support and promote my research using hybrid experimental and computational approaches to better understand TTFields therapy response. This early-career investigator support is invaluable for establishing my career as a cancer researcher.
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.