Interconnected Adaptive Responses: A Way Out for Cancer Cells to Avoid Cellular Demise

SIMPLE SUMMARY: One of the major obstacles to anti-cancer therapy is the development of drug resistance that allows the cancer cell to adapt to the treatments and keep surviving. In this mini-review we attempt to give an overview of the adaptive responses and the cross-talk between them that could be targeted to counteract cancer resistance to stress and improve the outcome of cancer treatment. ABSTRACT: Different from normal cells, cancer cells must hyperactivate a variety of integrated responses in order to survive their basal stress or its exacerbation caused by exposure to anti-cancer agents. As cancer cells become particularly dependent on these adaptive responses, namely UPR, DDR autophagy, anti-oxidant and heat shock responses, this turns out to be an Achille’s heel, which allows them to be selectively killed while sparing normal unstressed cells. Better knowledge of the cross-talk between these adaptive processes and their impact on the immune system is needed to design more effective anti-cancer therapies, as reviewed in this paper.