Synta Pharmaceuticals Corp. (NASDAQ: SNTA) today announced the launch of its Hsp90-inhibitor Drug Conjugate (HDC) platform, which leverages the Company’s expertise in chaperone biology and medicinal chemistry to create a new class of anti-cancer therapies.
The need: delivering potent anti-cancer drugs directly to tumors
Current oncology therapeutics generally fall into two categories: cytotoxic agents and molecularly targeted therapies. Cytotoxic agents are often broadly active, but have the disadvantage of high toxicity caused by damage to normal cells, which limits their utility. Drugs that target specific protein drivers of cancer cell growth are generally more tumor selective, yet often lead to tumor resistance via point mutations in their target (e.g. ALK, BRAF, EGFR inhibitors) or activation of alternative signaling pathways (e.g., MEK, ERK, or AKT upregulation).
Targeted delivery strategies, such as Antibody Drug Conjugates (ADCs), offer a solution to these limitations by delivering potent anti-cancer payloads more directly to tumors. HDCs offer many of the advantages of antibody-driven targeted delivery with potentially broader applicability. Because of its unique properties, Hsp90 (heat shock protein 90) may represent one of the most compelling targets for delivering drug payloads to tumors.
HDCs exploit the preferential accumulation of Hsp90-inhibitors in tumors to increase the selective delivery of anti-cancer payloads
Hsp90 is a chaperone protein required by many cancer cells to maintain the stability and function of numerous proteins that drive cancer cell growth, survival, and metastasis. Small molecule inhibitors of Hsp90, including Synta’s drug candidate ganetespib as well as first-generation inhibitors such as 17-AAG and its derivatives, are retained in tumors for as much as 20 times longer than in blood or normal tissue [1, 2]. These properties are believed to be due to overexpression of an active form of Hsp90 in cancer cells as compared to normal tissues, and have been recently applied for tumor imaging [3, 4].