Promising Kidney Cancer Treatment Targets Calcium Imbalance Caused by Tumors

Elevated blood calcium levels, a common complication in advanced kidney cancer known as hypercalcemia, pose significant health risks including confusion, muscle spasms, and seizures. This condition is often associated with lower survival rates among patients. Traditionally, hypercalcemia is managed using drugs like bisphosphonates, which work to reduce calcium release from bones. However, these medications can cause side effects such as osteonecrosis of the jaw, fractures, and can even lead to hypocalcemia, a condition characterized by excessively low blood calcium levels.

Recent research conducted by a team at UT Southwestern Medical Center offers new hope for treating hypercalcemia directly at its source. The study focused on HIF-2α inhibitors—medications developed to block a protein involved in cancer progression. The research team, led by investigator James Brugarolas, Ph.D., evaluated whether these inhibitors could effectively control hypercalcemia caused by kidney tumors.

Many kidney cancers produce a hormone called parathyroid hormone-related protein (PTHrP), which significantly raises blood calcium levels. Prior studies indicated that the production of PTHrP in kidney cancer is regulated by HIF-2, pointing to the potential of HIF-2α inhibitors in managing hypercalcemia. The development of these drugs traces back to discoveries in the 1990s that identified HIF-2α as a key component in tumor growth, leading to the creation of effective drugs like PT2399 and the FDA-approved belzutifan (PT2977).

In laboratory studies, researchers transplanted human kidney tumors into mice and treated those with hypercalcemia using PT2399. Most mice responded positively; their calcium levels dropped sharply within days, and symptoms such as weight loss and fatigue lessened. Further analysis revealed that PT2399 prevents HIF-2α from binding to the gene responsible for producing PTHrP, thereby reducing its levels and alleviating hypercalcemia.

Additionally, a case study involving a 63-year-old patient with advanced clear cell renal cell carcinoma and high calcium levels demonstrated the drug’s effectiveness. Treatment with belzutifan resulted in a quick decrease in PTHrP and normalization of calcium levels, all without the adverse side effects often seen with traditional therapies.

Dr. Brugarolas emphasized the potential of these findings, stating, "Our study supports the systematic evaluation of HIF-2α inhibitors for kidney cancer patients suffering from hypercalcemia." This research signals a promising new approach to managing a dangerous complication of kidney cancer, potentially improving both patient outcomes and quality of life.

Source: https://medicalxpress.com/news/2025-10-kidney-cancer-drug-dangerous-calcium.html