The molecular pathogenesis of small cell lung cancer

Abstract

Small cell lung cancer (SCLC) represents 13% of all lung cancer cases diagnosed in the United States. Although a chemotherapy and radiation-sensitive disease, SCLC recurs rapidly with only 5% of patients surviving five years. This dismal prognosis likely is secondary to few improvements in its treatment, without significant changes in its standard of care over the last three decades. SCLC has a unique biology with specific molecular and cellular changes, which are the subject of active investigation. Here, we summarize the alterations leading to the pathogenesis of SCLC: chromosomal changes; dysregulation of tumor suppressor genes, oncogenes, and signaling pathways; upregulation of receptor tyrosine kinases, growth factors and cellular markers; and the persistence of developmental pathways. Each of these represents potential targets for therapy and many biologic agents are being studied.

Genomic Landscape Survey Identifies SRSF1 as a Key Oncodriver in Small Cell Lung Cancer

“…Our results confirmed key oncogenic genes with recurrent CN gains/amplifications that were previously reported in SCLC [3,5,15,16,17], including MYC (8%), KIT (16%), and SOX2 (67%). Significant copy number gains or amplifications were observed across a cluster on chromosome 3q26-29 [5] (S5 Table).…”

Targeting Small Cell Lung Cancer Harboring PIK3CA Mutation with a Selective Oral PI3K Inhibitor PF-4989216

“…Although SCLC initially responds to chemotherapy and radiotherapy, it recurs rapidly with only 5% of patients surviving 5 years. Response to second-line chemotherapy for patients with refractory disease is less than 10%, and survival is 3 to 4 months (22,23). Multiple phase III trials have been conducted; however, the survival of patients with SCLC has not improved significantly over the years (24,25).…”

Elevated expression of TGIF is involved in lung carcinogenesis

“…A growing number of evidence indicates that risk factors for human lung cancer include cigarette smoking, occupational and environmental exposures to secondhand smoke, asbestos, certain metals, some organic chemicals and radiation, and specific genetic alterations [3][4][5][6][7][8]. To our knowledge, pathogenesis of lung cancer is complicated and associated with activation of oncogenes, inactivation of tumor suppressor genes, and dysregulation of cellular signaling pathways [9][10][11][12]. The underlying molecular mechanisms responsible for lung carcinogenesis have not yet been clearly elucidated.…”