AUY922 + erlotinib

AUY922 + erlotinib is a combination therapy consisting of the small molecule HSP90 inhibitor AUY922 (also known as NVP-AUY922) and the EGFR tyrosine kinase inhibitor erlotinib. This combination was investigated primarily for patients with non-small cell lung cancer (NSCLC) harboring EGFR mutations who developed acquired resistance to first-line EGFR TKI therapy. - **AUY922** inhibits heat shock protein 90 (HSP90), leading to degradation of client oncoproteins including mutant epidermal growth factor receptor (EGFR), which is implicated in tumor growth and survival. - **Erlotinib** is an oral small molecule that selectively inhibits the tyrosine kinase activity of EGFR, blocking downstream signaling pathways involved in cell proliferation and survival. The rationale for combining these agents was to overcome resistance mechanisms—such as secondary mutations like T790M—in patients progressing on single-agent EGFR TKIs by targeting both the chaperone machinery stabilizing mutant proteins (via HSP90 inhibition) and direct kinase inhibition. In clinical studies, this combination showed partial responses but was limited by toxicities such as night blindness, diarrhea, skin rash, hyperglycemia, liver enzyme elevations, hypoalbuminemia, hyponatremia, lymphopenia, nausea, fatigue. The phase II trial did not meet its primary endpoint for response rate improvement over monotherapy[1][4][5].

Other names

AUY922 and erlotinibAUY-922 and erlotinibAUY 922 and erlotinibHSP90 inhibitor AUY922 and erlotinib hydrochlorideHSP-90 inhibitor AUY922 and erlotinib hydrochlorideHSP 90 inhibitor AUY922 and erlotinib hydrochloride