Which substance is primarily responsible for causing hypercalcemia in malignancy?

Explanation

Hypercalcemia in cancer patients is most commonly caused by the secretion of parathyroid hormone-related protein (PTHrP), which mimics the effects of parathyroid hormone and leads to increased calcium levels. While PTH, IL-6, and calcitonin can influence calcium metabolism, PTHrP is the predominant mediator in malignancy-associated hypercalcemia.