Beyond adenocarcinoma: current treatments and future directions for squamous, small cell, and rare lung cancer histologies

David E. Gerber, Paul K. Paik, Afshin Dowlati

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9 Citations (Scopus)

Abstract

Lung cancer encompasses a diverse spectrum of histologic subtypes. Until recently, the majority of therapeutic advances were limited to the minority of patients with adenocarcinoma. With the advent of comprehensive genomic profiling of squamous and small cell lung cancers, new therapeutic targets have emerged. For squamous tumors, the most promising of these include fibroblast growth factor receptor (FGFR), the phosphatidylinositol 3-kinase (PI3K) pathway, discoidin domain receptor 2 (DDR2), and G1/S checkpoint regulators. In 2014, the antiangiogenic agent ramucirumab was approved for all non-small cell lung cancer (NSCLC) histologies, including squamous tumors. Immunotherapeutic approaches also appear to be promising for these cases. Genomic analysis of small cell lung cancer has revealed a high mutation burden, but relatively few druggable driver oncogenic alterations. Current treatment strategies under investigation are focusing on targeting mitotic, cell cycle, and DNA repair regulation, as well as immunotherapy. Pulmonary neuroendocrine tumors represent a diverse spectrum of diseases that may be treated with somatostatin analogs, cytotoxic agents, and molecularly targeted therapies. Radiolabeled somatostatin analogs and combinations with mammalian target of rapamycin (mTOR) inhibitors also show potential. Large cell neuroendocrine tumors share numerous clinical, pathologic, and molecular features with small cell lung cancer; however, whether they should be treated similarly or according to a NSCLC paradigm remains a matter of debate.

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Small Cell Lung Carcinoma
Histology
Adenocarcinoma
Epithelial Cells
Neuroendocrine Tumors
Somatostatin
Non-Small Cell Lung Carcinoma
Phosphatidylinositol 3-Kinase
Fibroblast Growth Factor Receptors
Squamous Cell Neoplasms
Angiogenesis Inhibitors
Cytotoxins
Sirolimus
Therapeutics
DNA Repair
Immunotherapy
Lung Neoplasms
Neoplasms
Cell Cycle
Lung

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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abstract = "Lung cancer encompasses a diverse spectrum of histologic subtypes. Until recently, the majority of therapeutic advances were limited to the minority of patients with adenocarcinoma. With the advent of comprehensive genomic profiling of squamous and small cell lung cancers, new therapeutic targets have emerged. For squamous tumors, the most promising of these include fibroblast growth factor receptor (FGFR), the phosphatidylinositol 3-kinase (PI3K) pathway, discoidin domain receptor 2 (DDR2), and G1/S checkpoint regulators. In 2014, the antiangiogenic agent ramucirumab was approved for all non-small cell lung cancer (NSCLC) histologies, including squamous tumors. Immunotherapeutic approaches also appear to be promising for these cases. Genomic analysis of small cell lung cancer has revealed a high mutation burden, but relatively few druggable driver oncogenic alterations. Current treatment strategies under investigation are focusing on targeting mitotic, cell cycle, and DNA repair regulation, as well as immunotherapy. Pulmonary neuroendocrine tumors represent a diverse spectrum of diseases that may be treated with somatostatin analogs, cytotoxic agents, and molecularly targeted therapies. Radiolabeled somatostatin analogs and combinations with mammalian target of rapamycin (mTOR) inhibitors also show potential. Large cell neuroendocrine tumors share numerous clinical, pathologic, and molecular features with small cell lung cancer; however, whether they should be treated similarly or according to a NSCLC paradigm remains a matter of debate.",
author = "Gerber, {David E.} and Paik, {Paul K.} and Afshin Dowlati",
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AU - Paik, Paul K.

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