ridaforolimus + MK-0752

A combination of **ridaforolimus**, an mTOR inhibitor, and **MK-0752**, a gamma-secretase inhibitor targeting Notch signaling, investigated primarily as an oral regimen for advanced solid tumors. Ridaforolimus blocks the mammalian target of rapamycin (mTOR) pathway, inhibiting tumor cell growth and proliferation. MK-0752 inhibits the Notch signaling pathway, disrupting cancer cell maintenance and proliferation especially when Notch signaling aberrantly activates the PI3K-AKT-mTOR axis. The combination aimed to achieve complementary blockade of key oncogenic pathways, with preclinical rationale suggesting enhanced antitumor effect. Clinical evaluation reached phase 1, primarily in adults with advanced or metastatic solid tumors, with preliminary evidence of antitumor activity observed especially in head and neck squamous cell carcinoma (HNSCC); however, the combination was associated with a high rate of dose-limiting toxicities—primarily stomatitis, diarrhea, and asthenia—necessitating careful management and dose adjustment[1][2][3].