A new clinical trial will investigate the safety of vantictumab (OMP-18R5), a new lung cancer drug targeting cancer stem cells (CSCs). CSCs, the actively multiplying cells responsible for generating tumors, are thought to be central in cancer relapse by ‘repopulating’ tumors, even if the bulk of the tumors cells are destroyed during treatment. Vantictumab blocks the Wnt pathway, a key molecular signaling pathway used by CSCs. Patients with previously treated advanced non-small cell lung cancer (NSCLC) will receive vantictumab in combination with the chemotherapy agent docetaxel (Taxotere). In addition to the safety of the drug combination, the trial will also investigate how effective it is and whether any biomarkers predict how well patients respond.
“Human benign nevi (moles) are clonal neoplasms that rarely progress to melanoma because their cells (melanocytes) are arrested in a viable but nonproliferating state (senescence). However, at low frequency, nevus melanocytes do progress to melanoma. Consequently, it is important to understand the factors that determine nevus formation and progression to melanoma. We present evidence that repression of a proliferation-promoting cell signaling pathway (Wnt signaling pathway) contributes to senescence of melanocytes in vitro. However, Wnt signaling remains active in some senescent human melanocytes in nevi, and activation of Wnt signaling leads to a delay in melanocyte senescence in a mouse model. We suggest that activated Wnt signaling in human nevi delays senescence to promote nevus formation, and thereafter, persistent Wnt signaling might undermine senescence-mediated tumor suppression.”