Targeting apoptosis pathways in lung cancer.
Lung cancer is a devastating disease with a poor prognosis. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) represent different forms of lung cancer that are associated with distinct genetic causes and display different responses to therapy in the clinic. Whereas SCLC is often sensitive to chemotherapy at start of treatment, NSCLC are less chemo-sensitive. In NSCLC different histological subtypes are distinguished and increasing efforts are made to identify subtypes that respond to specific therapies, such as those harbouring epidermal growth factor receptor (EGFR) mutations that have benefit from treatment with EGFR inhibitors. Targeting of the apoptotic machinery represents another approach that aims to selectively kill cancer cells while sparing normal ones. Here we describe different ways that are currently explored to induce apoptosis in lung cancer cells, specifically pathways controlled by TNF-related apoptosis-inducing ligand (TRAIL), BCL-2 family members and apoptosis inhibitory proteins (IAPs). Preclinical studies are discussed and for some agents results from early clinical studies and future perspectives are considered.
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Milind M
MM
Pore
T Jeroen N
TJ
Hiltermann
Frank A E
FA
Kruyt
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D066246:ErbB Receptors / Q000235:genetics; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000188:drug therapy / Q000473:pathology*; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051636:X-Linked Inhibitor of Apoptosis Protein; D066246:ErbB Receptors