Abstract B038: Blockade of c-met signaling to circumvent radioresistance-associated metastasis in head and neck cancer

Abstract

Abstract One of the significant clinical challenges in head and neck cancer (HNC) treatment is a high rate of recurrence and metastasis after radiotherapy. Once tumor metastasis occurs following radiotherapy, the prognosis of HNC patients is extremely poor. However, the failure of radiotherapy for cancers is closely related to various factors, and the underlying mechanism remains unclear. We report here that c-Met is the most activated receptor tyrosine kinases in HNC cells once they develop radioresistance. Inactivation of c-Met dramatically attenuates the increased metastatic potential gained in HNC radioresistant cells, leading to tumor regression. Cancer stem cells (CSC) have been confirmed to be in a quiescent state in most established tumors. Mechanistically, the quiescent CSC population can be “awakened” by hyperactive c-Met signaling in radiation, which in turn initiates proliferation and differentiation to potentiate a series of malignant phenotypes. Most importantly, knockdown c-Met by shRNAs or inactivating it by c-Met inhibitor SU11274 reduces the population of “awakened” CSCs and suppresses metastasis, leading to increased sensitivity of HNC radioresistant cells to radiation. These novel findings highlight the importance of additional c-Met blockade in radiotherapy and suggest that combined targeting of c-Met and radiotherapy could be a promising strategy to improve the care for patients with HNC. Citation Format: Juan Dou, Liwei Lang, Georgia Chen, Nabil F. Saba, Yong Teng. Blockade of c-met signaling to circumvent radioresistance-associated metastasis in head and neck cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B038.