Leveraging microenvironmental synthetic lethalities to treat cancer
| Autor: | Kevin J. Metcalf, Alaa Alazzeh, Valerie M. Weaver, Zena Werb |
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| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine Immunology Drug Resistance Cancer therapy Synthetic lethality Medical and Health Sciences 03 medical and health sciences Rare Diseases 0302 clinical medicine Stroma Neoplasms Tumor Microenvironment Animals Humans Medicine Molecular Targeted Therapy Cancer Tumor microenvironment business.industry Review Series General Medicine Therapeutic resistance medicine.disease Good Health and Well Being 030104 developmental biology Drug Resistance Neoplasm 5.1 Pharmaceuticals Tumor progression 030220 oncology & carcinogenesis Disease Progression Cancer research Neoplasm Female Immunotherapy sense organs Development of treatments and therapeutic interventions Signal transduction Synthetic Lethal Mutations business Signal Transduction |
| Zdroj: | The Journal of clinical investigation, vol 131, iss 6 J Clin Invest |
| ISSN: | 1558-8238 0021-9738 |
| Popis: | Treatment resistance leads to cancer patient mortality. Therapeutic approaches that employ synthetic lethality to target mutational vulnerabilities in key tumor cell signaling pathways have proven effective in overcoming therapeutic resistance in some cancers. Yet, tumors are organs composed of malignant cells residing within a cellular and noncellular stroma. Tumor evolution and resistance to anticancer treatment are mediated through a dynamic and reciprocal dialogue with the tumor microenvironment (TME). Accordingly, expanding tumor cell synthetic lethality to encompass contextual synthetic lethality has the potential to eradicate tumors by targeting critical TME circuits that promote tumor progression and therapeutic resistance. In this Review, we summarize current knowledge about the TME and discuss its role in treatment. We outline the concept of tumor cell–specific synthetic lethality and describe therapeutic approaches to expand this paradigm to leverage TME synthetic lethality to improve cancer therapy. |
| Databáze: | OpenAIRE |
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