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Updated: Jul 18, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
New insights into RAS in head and neck cancer
Sankar Jagadeeshan1, Ofra Z Novoplansky1, Oded Cohen2
1The 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.
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.
Insights
RAS gene alterations are crucial in head and neck cancer (HNC) development and progression. Targeting these RAS alterations offers potential therapeutic strategies for HNC patients, impacting tumor growth and therapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Genetics
Background:
- RAS genes are frequently dysregulated in various cancers.
- RAS pathway alterations are implicated in head and neck cancer (HNC) initiation and progression.
- Recent development of RAS inhibitors underscores the need to understand RAS roles in HNC.
Purpose of the Study:
- To review and summarize published findings on RAS alterations and pathway activations in HNC.
- To elucidate the role of RAS in HNC initiation, progression, and metastasis.
- To explore the potential of targeting RAS in HNC therapy.
Main Methods:
- Systematic review of published literature on RAS alterations in HNC.
- Analysis of RAS gene mutations, pathway activations, and their clinical implications.
- Examination of RAS's role in tumor cell signaling, tumor microenvironment (TME), and therapy resistance.
Main Results:
- RAS alterations play a significant role in HNC initiation, progression, and metastasis.
- Mutated RAS intrinsically affects tumor cell signaling and extrinsically influences TME heterogeneity, including angiogenesis and immune escape.
- RAS alterations contribute to therapy resistance, both intrinsically and extrinsically.
Conclusions:
- Understanding RAS alterations in HNC is critical for developing effective treatments.
- Targeting RAS, as a single agent or in combination therapies, shows promise for HNC patients with RAS-activated tumors.
- RAS pathway modulation could overcome therapy resistance in HNC.
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