Indication: Cancer

Indication Target/marker/pathway Summary Licensing status Publication and contact information
Pancreatic cancer Actin a2 smooth aorta muscle (ACTA2; a-SMA); smoothened (SMO); sonic hedgehog homolog (SHH) Studies in mice and patients suggest depleting tumor stroma and fibrosis could be deleterious as opposed to helpful in treating pancreatic cancer. Past studies suggested tumor stroma and fibrosis impede drug delivery in patients with pancreatic ductal adenocarcinoma (PDAC). Thus, stroma- and fibrosis-depleting compounds such as hedgehog pathway inhibitors were pursued in the indication as potential complements to chemotherapy. In genetic mouse models of PDAC, depletion of a-Sma+ stromal myofibroblasts, knocking out Shh or blocking hedgehog signaling with the SMO inhibitor saridegib all decreased tumor stroma and fibrosis but resulted in the development of a more aggressive disease phenotype and decreased survival compared with what was seen in control mice. In a cohort of 53 patients with PDAC, low levels of the myofibroblast marker a-SMA were associated with decreased overall survival (p=0.0053). Next steps include elucidating the role of various stromal cell populations in PDAC and determining whether there are specific scenarios in which stroma- and fibrosis-depleting drugs such as SMO inhibitors could have benefit. Infinity Pharmaceuticals Inc. discontinued saridegib in 2012 after interim data from the

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