The AACR-Novocure Tumor Treating Fields Research Grants represent a joint effort to promote and support innovative research focused on Tumor Treating Fields (TTFields), which are intermediate frequency, low intensity, alternating electric fields that disrupt cell division in cancer cells. 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. Funded research must be focused on the preclinical application of TTFields in cancer and may be basic or translational in nature.

2024 grantees

Research

Treatment for the deadly brain tumor glioblastoma (GBM) has been improved through the non-invasive addition of alternating electric fields, known as tumor treating fields (TTFields).  Through kinomic profiling of temozolomide-sensitive and temozolomide-resistant GBM cells, the Hjelmeland and Willey laboratories identified kinases which are predicted to be impacted by TTFields. Addition of the kinase inhibitor crenolanib to TTFields was found to further decrease GBM cell growth.  Dr. Hjelmeland seeks to expand these findings by characterizing additional kinase-mediated mechanisms of TTFields resistance and sensitivity in the context of GBM chemo- and radioresistance. 

Biography

Dr. Hjelmeland obtained her doctorate in pharmacology and cancer biology from Duke University and completed a postdoctoral fellowship neuro-oncology, also at Duke University.  She was on staff at the Cleveland Clinic before starting her laboratory at the University of Alabama at Birmingham (UAB).  Dr. Hjelmeland is the Basic Science Co-Leader of the Neuro-Oncology Program of the O’Neal Comprehensive Cancer Center and Associate Professor of Cell, Developmental and Integrative Biology at UAB.   Her laboratory is focused on identifying novel mechanisms promoting glioblastoma growth and therapeutic resistance that can be targeted to improve patient outcomes.  

Acknowledgment of Support

“We sincerely appreciate the support from AACR and Novocure through the 2024 AACR-Novocure Cancer Research Grant.  These funds will allow us to move forward with our efforts to identify blood brain barrier penetrant kinase inhibitors that improve the efficacy of TTFields in primary and/or recurrent GBM cells.” 

Research

Preliminary in vitro data have shown promising effects of Tumor Treating Fields (TTFields) on both morphological and functional aspects of the glioblastoma network. Dr. Ratliff aims to investigate the biological effects of TTFields on critical drivers of glioblastoma malignancy, with a particular emphasis on tumor microtube formation and the function and integrity of the glioblastoma tumor cell network. They plan to analyze these effects from morphological, functional, transcriptional, and metabolomic perspectives using glioblastoma brain organoids and in vivo chronic cranial window mouse models. In addition, her study builds on a recently established and clinically validated connectivity signature for glioblastoma, identified as a robust biomarker associated with the mesenchymal expression subtype, TP53 wild-type status, and poor patient survival. They plan to investigate the effects of TTFields on this connectivity signature and provide new insights into the potential of TTFields as a therapeutic strategy for glioblastoma.

Biography

Dr. Ratliff is a dedicated neurosurgeon with over a decade of experience in neuro-oncology. In addition to her medical training, she holds a graduate degree in biology, providing her with a strong foundation in molecular biology and scientific methodology. She received further training in the research group of Professor Winkler at the German Cancer Research Center (DKFZ), where she contributed to establishing a molecular focus and implementing intravital microscopy techniques. Dr. Ratliff has since established her own research group and laboratory at the University Medical Center Mannheim, Germany, benefiting from research associations that provide extensive resources and collaborative opportunities.

Acknowledgement of Support

“Receiving the 2024 AACR-Novocure Cancer Research Grant will allow me to investigate whether TTFields target the glioblastoma tumor cell network, a focus of several ongoing clinical trials. As a neurosurgeon, devoting more time to research fulfills my passion and advances my academic and scientific career.”