Dysregulation of calcium homeostasis in cancer and its role in chemoresistance

Globally, cancer, as a major public health concern, poses a severe threat to people's well-being. Advanced and specialized therapies can now cure the majority of people with early-stage cancer. However, emerging resistance to traditional and novel chemotherapeutic drugs remains a serious issue in clinical medicine. Chemoresistance often leads to cancer recurrence, metastasis, and increased mortality, accounting for 90% of chemotherapy failures. Thus, it is important to understand the molecular mechanisms of chemoresistance and find novel therapeutic approaches for cancer treatment. Among the several factors responsible for chemoresistance, calcium (Ca ) dysregulation plays a significant role in cancer progression and chemoresistance. Therefore, targeting this derailed Ca signalling for cancer therapy has become an emerging research area. Of note, the Ca signal and its proteins are a multifaceted and potent tool by which cells achieve specific outcomes. Depending on cell survival needs, Ca is either upregulated or downregulated in both chemosensitive and chemoresistant cancer cells. Consequently, the appropriate treatment should be selected based on Ca signalling dysregulation. This review discusses the role of Ca in cancer cells and the targeting of Ca channels, pumps, and exchangers. Furthermore, we have emphasised the role of Ca in chemoresistance and therapeutic strategies. In conclusion, targeting Ca signalling is a multifaceted process. Methods such as site-specific drug delivery, target-based drug-designing, and targeting two or more Ca proteins simultaneously may be explored; however, further clinical studies are essential to validate Ca blockers' anti-cancer efficacy.