New insights into RAS in head and neck cancer

Sankar Jagadeeshan; Ofra Z Novoplansky; Oded Cohen; Ina Kurth; Jochen Hess; Ari J Rosenberg; Jennifer R Grandis; Moshe Elkabets

doi:10.1016/j.bbcan.2023.188963

New insights into RAS in head and neck cancer

Biochim Biophys Acta Rev Cancer. 2023 Nov;1878(6):188963. doi: 10.1016/j.bbcan.2023.188963. Epub 2023 Aug 22.

Authors

Sankar Jagadeeshan¹, Ofra Z Novoplansky², Oded Cohen³, Ina Kurth⁴, Jochen Hess⁵, Ari J Rosenberg⁶, Jennifer R Grandis⁷, Moshe Elkabets⁸

Affiliations

¹ The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel. Electronic address: sankariitj@gmail.com.
² The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel. Electronic address: ofranovo@gmail.com.
³ Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel; Department of Otolaryngology- Head and Neck Surgery and Oncology, Soroka Medical Center, Beersheva, Israel. Electronic address: oded915@gmail.com.
⁴ Division of Radiooncology-Radiobiology, German Cancer Research Center (DKFZ), Heidelberg, Germany. Electronic address: ina.kurth@dkfz-heidelberg.de.
⁵ Department of Otorhinolaryngology, Head and Neck Surgery, Heidelberg University Hospital, 69120 Heidelberg, Germany; Molecular Mechanisms of Head and Neck Tumors, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. Electronic address: Jochen.Hess@med.uni-heidelberg.de.
⁶ Department of Medicine, Section of Hematology and Oncology, University of Chicago, Chicago, IL, USA. Electronic address: arirosenberg@bsd.uchicago.edu.
⁷ Department of Otolaryngology - Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA. Electronic address: Jennifer.Grandis@ucsf.edu.
⁸ The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel; Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O.B. 653, Beer-Sheva 8410501, Israel. Electronic address: moshee@bgu.ac.il.

PMID: 37619805
DOI: 10.1016/j.bbcan.2023.188963

Abstract

RAS genes are known to be dysregulated in cancer for several decades, and substantial effort has been dedicated to develop agents that reduce RAS expression or block RAS activation. The recent introduction of RAS inhibitors for cancer patients highlights the importance of comprehending RAS alterations in head and neck cancer (HNC). In this regard, we examine the published findings on RAS alterations and pathway activations in HNC, and summarize their role in HNC initiation, progression, and metastasis. Specifically, we focus on the intrinsic role of mutated-RAS on tumor cell signaling and its extrinsic role in determining tumor-microenvironment (TME) heterogeneity, including promoting angiogenesis and enhancing immune escape. Lastly, we summarize the intrinsic and extrinsic role of RAS alterations on therapy resistance to outline the potential of targeting RAS using a single agent or in combination with other therapeutic agents for HNC patients with RAS-activated tumors.

Keywords: Head and neck cancer; Metastasis; Pre-clinical and clinical targeting; Progression; RAS activation; Therapy resistance.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Genes, ras
Head and Neck Neoplasms* / drug therapy
Head and Neck Neoplasms* / genetics
Humans
Signal Transduction
Tumor Microenvironment

Substances

Antineoplastic Agents