Senolytics : Eliminating therapy-induced senescence in cancer and alleviating consequent premature aging

초록

Clinical data show that anticancer treatments (e.g., genotoxic and cytotoxic drugs) have the ability to induce senescent phenotypes in a subset of treated tumor cells. This type of cellular senescence is termed therapy-induced senescence (TIS). Cellular senescence is considered to be a tumor suppressor mechanism that halts the proliferation of oncogene-activated cells and malignant cells. But there is accumulating evidence showing TIS cells can escape the senescence program to re-enter the cell cycle to resist anticancer treatment. TIS cells contribute to local and systemic inflammation, via their senescence-associated secretory phenotype (SASP) to induce cancer relapse and accelerated aging phenotypes (e.g., frailty, sarcopenia, and cognitive impairment). Thus, it becomes important to understand the contributions of senescent cells and their secreted SASP to chronic inflammation and consequent premature aging and to develop senolytics (i.e., compounds that selectively eliminate senescent cells (e.g., JQ1)). This talk will cover these points and senolytic drugs to potentially reduce accelerated aging as a consequence of cancer treatment.