Role of Adding Hydroxychloroquine to Chemotherapy in Patients with Neoplasia

Abstract

Cancer remains the second leading cause of death globally, with approximately 10 million deaths reported in 2020. Despite advances in treatment modalities, the toxicity and limited efficacy of conventional chemotherapy necessitate the exploration of adjuvant strategies to enhance therapeutic outcomes. Hydroxychloroquine (HCQ), a synthetic antimalarial drug derived from quinine, has emerged as a promising adjuvant agent in cancer therapy due to its autophagy-inhibiting properties and favorable safety profile. This review examines the role of adding hydroxychloroquine to chemotherapy in patients with neoplasia, focusing on its mechanisms of action and clinical potential. HCQ exerts anticancer effects through multiple pathways, including autophagy inhibition, enhancement of apoptosis, tumor vasculature normalization, reduction of cancer stem cells, and modulation of immune responses by repolarizing tumor-associated macrophages. Preclinical studies have demonstrated synergistic effects when HCQ is combined with various chemotherapeutic agents, radiation therapy, and targeted therapies. Early-phase clinical trials combining HCQ with temozolomide, temsirolimus, and vorinostat have shown tolerability and preliminary evidence of autophagy modulation, though optimal dosing and reliable biomarkers remain challenging. While HCQ presents a cost-effective and well-tolerated option for augmenting chemotherapy efficacy, further research is needed to establish its clinical benefit and identify patient populations most likely to respond to this combinatorial approach.