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Inactivation of DNA repair mechanism impairs tumour growth

Molecular alterations in DNA mismatch repair (MMR) lead to an increased mutational load and accumulation of neoantigens in cancer cells, which correlates with positive response to immunotherapy. In this study, the mouse cancer cell lines with genetically inactivated MutL homologue 1 (MLH1) gene were generated to obtain MMR defective clones. Tumour growth of MLH1 mutant cell lines was markedly impaired when injected in mice and presented improved immune surveillance.  Analogous results were obtained with a temozolomide (TMZ)-treated cancer cell line. Temozolomide is an approved drug for several types of cancer, which triggers DNA damage and affects DNA repair mechanisms.

For more details read the original paper published in Nature Letters: Germano et al., 2017.

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