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Journal of Thoracic Oncology • Volume 7, Number 12, Supplement 5, December 2012 Santa Monica Supplement Doubling Down with Inhibitors of Notch and Hedgehog Signaling Pathways Glen J. Weiss, MD he bulk of tumor is thought to be composed of differenti- in clinical trials that target the HHSP are inhibitors of SMO. Tated cancer cells, with only a small fraction consisting of To date, clinical results on at least three drugs that target NSP pluripotent self-renewing putative cancer stem cells (CSCs) and five drugs that target the HHSP have now been formally (1). Recurrence or progression of tumor after treatment is often presented at national meetings. A few of these agents were caused by growth and differentiation of the CSCs, enabled highlighted at this meeting. by increased signaling of Hedgehog (1) and Notch in CSCs (2). Preclinical studies report that CSCs are more resistant to NSP Targeting with γ-Secretase Inhibitors systemic radiotherapy than differentiated cancer cells that are Dr. Stewart provided some additional background on often observed in the bulk of tumor mass (2). Therefore, cura- Notch, stating that it is commonly expressed in non–small-cell tive therapy for advanced/metastatic lung cancer may require lung cancer (NSCLC), its expression is increased by hypoxia, doubling down, a two-pronged approach: cytotoxic or appropri- and CSCs, defined by aldehyde dehydrogenase
Journal of Thoracic Oncology – Wolters Kluwer Health
Published: Dec 1, 2012
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