Tumor lysis syndrome promotes cancer chemoresistance and relapse through AMPK inhibition

Cancer is a disease caused when cells divide uncontrollably and spread into surrounding tissues. There are different therapeutic modalities that control cancer growth, of which surgery, chemotherapy, and radiotherapy. Chemotherapy is a cancer treatment approach in which medications are used to inhibit cell proliferation and tumor multiplication, thus avoiding invasion and metastasis and thus eradicate cancer. One of the common complications associated with cancer chemotherapy is rapid lysis of expanding tumor cells, known as tumor lysis syndrome (TLS). TLS is associated with number of metabolic changes such as hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. Among the consequences of hyperuricemia, hyperkalemia, hyper-phosphatemia and hypocalcemia is the inhibition of 5 ' AMP-activated protein kinase (AMPK). Inhibition of AMPK induced different cancer chemo-resistance mechanisms such as cancer stem cells (CSCs), p-glycoproteins, Octamer-binding transcription factor 4 (OCT-4), homeobox protein NANOG, Kruppel-like factor 4 (KLF4) and immune microenvironment and thus leads to poor response to chemotherapy and even relapses after treatment. Our review aims to uncover new mechanisms underlying the metabolic consequences of tumor lysis on AMPK in tumor microenvironment. In this review, we also investigated the effect of AMPK on different cancer chemo-resistance mechanisms such as cancer stem cells, p-glycoproteins, OCT-4, NANOG, KLF4 and immune microenvironment.

Automated summary

Cancer is a disease characterized by uncontrollable cell division and spreading into surrounding tissues. Chemotherapy is an effective treatment approach that inhibits cell proliferation and tumor multiplication. However, tumor lysis syndrome, a common complication of chemotherapy, leads to metabolic changes and inhibits AMPK, resulting in chemo-resistance mechanisms and poor response to treatment. This review aims to uncover new mechanisms underlying the metabolic consequences of tumor lysis on AMPK in the tumor microenvironment and investigate its effects on various chemo-resistance mechanisms.