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.

2022 Grantee

Research  

Tumor treating fields (TTFields) have been shown to prolong median overall survival and increase the survival rate of glioblastoma patients, when combined with adjuvant chemotherapy. Yet, the mechanisms by which TTFields potentiate the effects of chemotherapy are not completely understood. TTFields have been shown to permeabilize cancer cell membranes, thereby increasing access of therapies and diagnostic probes into cancer cells. Dr. Patel’s lab is set to: identify cell-specific permeabilization frequencies of TTFields; determine the kinetics and durability of the cell membrane permeabilization effect under TTFields exposure; and quantitate the amount of chemotherapy that gains access into TTFields-exposed cancer cells.  

Biography  

Chirag Patel earned BS/MSE degrees in biomedical engineering from Johns Hopkins University prior to completing MD/PhD training at The University of Texas MD Anderson Cancer Center (MDACC) UTHealth Graduate School of Biomedical Sciences (GSBS) and McGovern Medical School. After adult neurology residency at UCLA, he completed his training at Stanford as a postdoctoral fellow in molecular imaging and clinical neuro-oncology fellow. After two years on faculty in the Stanford neurology and radiology departments, he was recruited to MDACC. He is an assistant professor of neuro-oncology and a McNair Scholar. He is also affiliated with the Neuroscience and Cancer Biology PhD programs at the GSBS.  

Acknowledgement of Support  

I am grateful to receive this critical early support in my career development that will also provide an opportunity for me to mentor trainees in the lab. As a result of this award, we can further the understanding of TTFields-induced cancer cell membrane permeabilization, which could result in improved delivery of anti-cancer therapies. 

2021 Grantees

Research
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.

Biography
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.

Research
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.

Biography
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.

2020 Grantee

Research
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.

Biography
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.

2019 grantee

Research
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.

Biography
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.