Chloroquine as a promising adjuvant chemotherapy together with sunitinib

Abstract

Chloroquine - a clinically available and cheap antimalarial drug - might have potential usefulness as adjuvant chemotherapy when combined with sunitinib, reports a preclinical study recently published online in Chemico-biological Interactions . Just few years after its FDA approval to be used in renal cell carcinoma, imatinib resistant gastrointestinal tumor and pancreatic neuroendocrine tumor, increasing studies shed light on the limited clinical efficacy of sunitinib as well as rapid development of resistant cells when used as monotherapy presumably through lysosomal sequestration. Abdel-Aziz and her colleagues now showed that chloroquine augments sunitinib anticancer activity in vitro human cancer cell lines of breast, colorectal, cervical, laryngeal, liver and prostate origin and in vivo in murine Ehrlich ascites carcinoma tumor model. Furthermore, Abdel-Aziz and her colleagues showed that chloroquine interrupts autophagic flux which was induced by sunitinib. They noted that chloroquine when combined with sunitinib showed further activation of apoptosis in cancer cells. The observed synergy was associated with increased nitric oxide level and reduced reactive oxygen species levels. The present findings warrant further studies to explore the safety profile of the combination regimen and its clinical usefulness in vivo and then controlled clinical trials.