Tumor-Secreted ADAMTSL4 Activates Latent TGFβ1 to Drive Cancer Cachexia.

Tumor-derived ADAMTSL4 is linked to cancer cachexia by activating TGFβ1 and promoting multiorgan wasting and fibrosis in preclinical models and patients.

• Why it matters: Cancer cachexia causes severe weight loss and lacks effective treatments, making understanding its mechanisms crucial for developing targeted therapies.
• What they did: Researchers identified ADAMTSL4 as a circulating factor associated with cachexia, demonstrated its role in converting non-cachexia tumors into cachexia-inducing tumors in mice, and showed that blocking ADAMTSL4 or TGFβ signaling reduces muscle wasting and fibrosis.
• The result: Targeting ADAMTSL4 may offer a selective therapeutic approach to mitigate cachexia-related wasting and fibrosis without systemic TGFβ pathway inhibition, potentially improving patient outcomes.