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AACR-Novocure Career Development Awards for Tumor Treating Fields Research

The AACR-Novocure Career Development Awards 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 novel anti-cancer treatment modality and to accelerate the development of new treatment strategies to advance therapeutic options for cancer.

2020 Grantees

Narasimha Kumar Karanam, PhD

Narasimha Kumar Karanam, PhD

Instructor
UT Southwestern Medical Center
Dallas, Texas
Harnessing E2F-Rb-CDK4/6 axis for novel combination therapy with TTFields

Research
Tumor treating fields (TTFields) are low-intensity, intermediate frequency, alternating electric fields that are applied to tumor regions and cells using non-invasive arrays. Initial mechanism described for TTFields-induced cell death has been via the disruption of mitosis and later it was found that 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 identified a novel role for TTFields through the CDK–Rb–E2F axis. The goal of this project is to explore TTFields-induced proteome and metabolome changes in lung and pancreatic cancers using in vitro and in vivo models. Moreover, this project will test novel combination therapy options targeting deregulated CDK–Rb–E2F axis using E2F and CDK4/6 inhibitors together with TTFields.

Biography
Dr. Karanam received his master’s degree in biochemistry from the University of Hyderabad, India. He then joined the Center for Cellular and Molecular Biology in Hyderabad, India, as a research assistant. This is where his interest in cancer research began. He subsequently pursued his PhD in cancer biology at the University of Greifswald, Germany, with Professor Uwe Volker. As a postdoctoral fellow in Dr. Michael Story’s laboratory, he examined the role of miRNAs in head and neck cancer progression. Dr. Karanam is currently an instructor at UT Southwestern Medical Center, where his research includes the interrogation of TTFields mechanisms of action for therapeutic benefit.

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.

Chirag B. Patel, MD, PhD

Chirag B. Patel, MD, PhD

Assistant Professor
Stanford University
Stanford, California
Increasing glioblastoma cell membrane permeability with TTFields

Research
The first demonstrated clinical efficacy of tumor treating fields (TTFields) was in glioblastoma. Compared to adjuvant chemotherapy alone, adjuvant chemotherapy and 200 kHz TTFields prolonged overall survival from 15 to 21 months and increased the 5-year survival rate from 5% to 13%. How TTFields potentiate the effects of chemotherapy against cancer is not completely understood. A recent finding that TTFields increase glioblastoma cell membrane permeability may help to explain some of the anti-cancer effects of TTFields. This project will (1) determine the optimal TTFields frequency for cell membrane permeabilization in glioblastoma and non-cancer cells; (2) identify the size of maximal membrane disruption due to TTFields; and (3) quantify the amount of chemotherapy entering and retained in glioblastoma upon TTFields exposure. If additional optimal TTFields frequency besides 200 kHz for disruption of glioblastoma cellular membrane integrity is found, then alternating it with the FDA-approved 200 kHz frequency may result in improved control in glioblastoma.

Biography
Dr. Patel earned BS/MSE degrees in biomedical engineering from Johns Hopkins University and MD/PhD degrees from the MD Anderson/UT-Houston Graduate School of Biomedical Sciences and UT-Houston Medical School. He completed adult neurology residency at the University of California, Los Angeles, and postdoctoral and clinical fellowships in molecular imaging and adult neuro-oncology, respectively, at Stanford University. He is now a clinical assistant professor of neurology and, by courtesy, of radiology at Stanford University. Dr. Patel’s laboratory studies the mechanisms of alternating electric fields (tumor treating fields [TTFields]) in human glioblastoma, with an aim to develop novel combination strategies for improved efficacy in this invariably lethal cancer.

Acknowledgment of Support
I am grateful to receive an AACR-Novocure Career Development Award for Tumor Treating Fields Research from the AACR and Novocure. This award will help me transition to independence by expanding on my previous studies focused on novel mechanisms of action of TTFields in glioblastoma, from a translational perspective.