BTE-EN1, which will be presented at AACR 2025, is a first-of-its-kind therapy which has demonstrated remarkable results in mouse studies, significantly reducing bone destruction and extending life in models of advanced prostate cancer. By targeting the complex interplay between cancer cells and bone, BTE-EN1 could offer a novel lifeline for patients facing one of the deadliest aspects of the disease.

BTE-EN1 is a heterobifunctional compound, a sophisticated molecule that combines two powerful components. One part, a selective inhibitor of cancer cell movement discovered in 2018, stops cancer cells from spreading within bone tissue. The other, a bisphosphonate group, binds tightly to bone mineral, ensuring the drug zeroes in on areas of bone destruction caused by prostate cancer metastasis. This dual-action approach disrupts the vicious cycle where cancer cells and bone cells fuel each other’s destructive behavior, leading to rapid bone loss.

In mouse studies, BTE-EN1 proved its mettle against well-established bone metastases. Using a cutting-edge model, researchers injected human prostate cancer cells directly into the leg bones of mice, allowing tumors to grow for two weeks to mimic advanced disease in patients. After six weeks of weekly BTE-EN1 treatments, CT imaging revealed a stunning 62% reduction in bone destruction compared to untreated mice. In a separate experiment, mice treated with BTE-EN1 before cancer cells were injected into their hearts—a model simulating widespread metastasis—lived significantly longer, with survival increasing in a dose-dependent manner.

Notably, traditional bone-protecting drugs like bisphosphonates and denosumab, commonly used in prostate cancer, failed to show similar survival benefits in these models.
What makes BTE-EN1 stand out is its safety and versatility. Lab tests confirmed that the drug retains the full potency of its two components, effectively blocking cancer cell movement while targeting bone lesions. Even at doses 4,000 times higher than those effective in mice, BTE-EN1 showed no toxicity, and it passed the NCI-60 cell line screen—a standard test for cancer drugs—with flying colors.

The drug also plays well with other prostate cancer treatments, showing no interference, and inhibits cell movement in various cancer types that destroy bone, hinting at broader potential.

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