Background Basal cell carcinoma (BCC) can arise by the uncontrolled proliferation of cells from multiple epidermal compartments due to aberrant activation Hedgehog (Hh) signalling pathway. Vismodegib, a small-molecule inhibitor this pathway, is approved for treatment patients with locally advanced (la) BCC inappropriate surgery or radiotherapy symptomatic metastatic (m) BCC. Objectives The aim ...

Nevoid basal cell carcinoma syndrome (NBCCS, Gorlin syndrome) is a rare genetic condition characterized by the early development of numerous cutaneous carcinomas (BCCs). Although most BCCs are surgically treated with total resection, some lesions may proceed to locally advanced or metastatic stage. Systemic treatment hedgehog inhibitors (HHIs) such as Vismodegib Sonidegib indicated in this popu...

Acquired resistance to targeted therapies threatens the value of these otherwise very promising agents. The recent description of resistance to the Hedgehog pathway inhibitor vismodegib (GDC-0449) in a medulloblastoma patient who had a dramatic initial response has spurred efforts to understand potential mechanisms of drug resistance. Elucidating these mechanisms will play a significant role in...

As a major regulatory pathway for embryonic development and tissue patterning, hedgehog signaling is not active in most adult tissues, but is reactivated in a number of human cancer types. A major milestone in hedgehog signaling in cancer is the Food and Drug Administration (FDA) approval of a smoothened inhibitor Vismodegib for treatment of basal cell carcinomas. Vismodegib can block ligand-me...

Tumor responses in advanced basal cell carcinoma (BCC) have been observed in clinical trials with vismodegib, a SMO antagonist. The result of SMO antagonism is inhibition Hedgehog Signaling Pathway (HHSP) downstream target genes. HHSP inhibition has been shown to affect stem cells responsible for blood, mammary, and neural development. We report on our experience of treating two patients with a...

Vismodegib (GDC-0449), an orally bioavailable small-molecule inhibitor of Hedgehog signaling, was recently approved by the U.S. Food and Drug Administration for the treatment of basal cell carcinoma that is either metastatic or locally advanced in patients who are not candidates for surgical resection or radiation. Given the absence of previously defined effective drug therapy for this disease,...

Although basal cell carcinoma (BCC) is the most common cancer worldwide, its metastatic dissemination is exceptional. Before 2012, we had a few treatment options available for metastatic or locally advanced cases. Management of these patients was complicated due to the lack of scientific data, the deterioration of a patient's general status, the patient's advanced age, and the presence of multi...

Abstract BACKGROUND The Hedgehog pathway directs gene expression programs that are essential for glioblastoma stem cells in vitro, but a clinical trial suggested inhibition does not improve outcomes (ABTC-0904). In pancreatic and bladder cancer, signaling through the tumor microenvironment induces stromal morphogens to inhibit cancer cell proliferation. Thus, we hypothesized may proliferation v...