The path to precision

St. Jude scientists have discovered a promising target for precision medicines to block a mechanism that drives several cancers, including the brain tumor medulloblastoma.

In about 30 percent of patients with medulloblastoma, a signaling pathway called Sonic Hedgehog is switched on by mistake. This causes cells to divide uncontrollably.

The researchers found that the Sonic Hedgehog pathway depends on another pathway that requires mTORC1 to function.

By blocking mTORC1 with a drug called INK128, the team disrupted the Sonic Hedgehog signaling pathway. INK128 is in clinical trials for treatment of another brain tumor and other solid tumors.

“The role of mTORC1 in the Hedgehog pathway was unexpected. It highlights the mTORC1 pathway as a potentially important molecular target for developing much-needed precision medicines for patients with the Sonic Hedgehog medulloblastoma subtype,” said Young-Goo Han, PhD, of St. Jude Developmental Neurobiology. “The results also raise hopes for combination targeted therapies to improve outcomes and ease treatment side effects.”

The findings appeared recently in the journal Developmental Cell.