AUTHOR=Ji Zhiwei , Moore Jade , Devarie-Baez Nelmi O. , Lewis Joshua , Wu Hanzhi , Shukla Kirtikar , Lopez Elsa I. Silva , Vitvitsky Victor , Key Chia-Chi Chuang , Porosnicu Mercedes , Kemp Melissa L. , Banerjee Ruma , Parks John S. , Tsang Allen W. , Zhou Xiaobo , Furdui Cristina M. 

TITLE=Redox integration of signaling and metabolism in a head and neck cancer model of radiation resistance using COSMRO

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.946320

DOI=10.3389/fonc.2022.946320

ISSN=2234-943X

ABSTRACT=<p>Redox metabolism is increasingly investigated in cancer as driving regulator of tumor progression, response to therapies and long-term patients’ quality of life. Well-established cancer therapies, such as radiotherapy, either directly impact redox metabolism or have redox-dependent mechanisms of action defining their clinical efficacy. However, the ability to integrate redox information across signaling and metabolic networks to facilitate discovery and broader investigation of redox-regulated pathways in cancer remains a key unmet need limiting the advancement of new cancer therapies. To overcome this challenge, we developed a new constraint-based computational method (COSM<sup>ro</sup>) and applied it to a Head and Neck Squamous Cell Cancer (HNSCC) model of radiation resistance. This novel integrative approach identified enhanced capacity for H<sub>2</sub>S production in radiation resistant cells and extracted a key relationship between intracellular redox state and cholesterol metabolism; experimental validation of this relationship highlights the importance of redox state in cellular metabolism and response to radiation.</p>