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Cancer therapeutic resistance occurs as cancers develop resistance to treatments such as chemotherapy, radiotherapy and targeted therapies, through many different mechanisms. These include specific genetic and epigenetic changes in the cancer cell and/or the microenvironment in which the cancer cell resides.
Post-translational modifications regulate tumorigenesis and cancer therapy sensitivity. Here, the authors show that N-glycosylation defective Interleukin-6 (deNG-IL6) switches downstream signalling pathway from JAK-STAT3 to SRC-YAP axis and lung cancer cells secrete deNG-IL6 to promote metastasis and tyrosine kinase inhibitor resistance.
Resistance to therapy remains the biggest challenge to achieving cures in patients with cancer. In this Roadmap, Russo et al. overview the field of cancer drug-tolerant persister cells providing paths to advance our understanding of their biology with innovative technologies and recommend strategies to therapeutically target them to ensure that more prolonged responses are achieved in patients with cancer.
KRAS G12C mutant selective inhibitors targeting inactive state have been approved for use in non-small cell lung cancer (NSCLC). Here, using models derived from a patient with NSCLC who progressed on sotorasib (KRAS G12C inhibitor), the authors identify increased KRAS GTP loading as an adaptive resistance mechanism which could be targeted with KRAS G12C inhibitors selective to the GTP active state.
Leighow et al. develop a strategy called the dual-switch selection gene drive platform, which enables the evolutionary dynamics of acquired resistance to be manipulated for therapeutic ends.
