A review of cancer-related hypercalcemia: Pathophysiology, current treatments, and future directions

Cancer-related hypercalcemia is a common metabolic complication seen in patients with advanced malignancies, affecting 10-30% of all cancer patients. It is associated with significant morbidity and mortality, highlighting the need for a comprehensive understanding of its pathophysiology and effective treatment strategies. The pathophysiology of cancer-related hypercalcemia involves the dysregulation of calcium homeostasis, primarily through the production of parathyroid hormone-related protein (PTHrP) by malignant cells. Moreover, it may associated to the stimulation of osteoclast activity resulting in increased bone resorption and release of calcium into the bloodstream. In addition, certain tumors can directly stimulate osteoclast activity and cause bone destruction. Dysregulation of renal calcium handling also contributes to hypercalcemia in cancer patients. However, future research directions in cancer-related hypercalcemia aimed to elucidate tumor-specific mechanisms, identify novel therapeutic targets, and develop personalized treatment approaches. Combination therapies, biomarkers, and predictive factors can enhance treatment efficacy and guide clinical decision-making. Furthermore, the focus on supportive care, psychosocial support, and palliative measures is essential to optimize patient comfort and quality of life. Improved imaging techniques, studies in pediatric populations, and investigations into long-term outcomes are also warranted. Advancements in these areas will contribute to better management and outcomes for cancer patients with hypercalcemia.