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Review
. 2015 May 15;21(10):2236-43.
doi: 10.1158/1078-0432.CCR-14-3039.

Squamous cell lung cancer: from tumor genomics to cancer therapeutics

David R Gandara  1 , Peter S Hammerman  2 , Martin L Sos  3 , Primo N Lara Jr  4 , Fred R Hirsch  5
Affiliations
Review

Squamous cell lung cancer: from tumor genomics to cancer therapeutics

David R Gandara et al. Clin Cancer Res. .

Abstract

Squamous cell lung cancer (SCC) represents an area of unmet need in lung cancer research. For the past several years, therapeutic progress in SCC has lagged behind the now more common non-small cell lung cancer histologic subtype of adenocarcinoma. However, recent efforts to define the complex biology underlying SCC have begun to bear fruit in a multitude of ways, including characterization of previously unknown genomic and signaling pathways, delineation of new, potentially actionable molecular targets, and subsequent development of a large number of agents directed against unique SCC-associated molecular abnormalities. For the first time, SCC-specific prognostic gene signatures and predictive biomarkers of new therapeutic agents are emerging. In addition, recent and ongoing clinical trials, including the Lung-MAP master protocol, have been designed to facilitate approval of targeted therapy-biomarker combinations. In this comprehensive review, we describe the current status of SCC therapeutics, recent advances in the understanding of SCC biology and prognostic gene signatures, and the development of innovative new clinical trials, all of which offer new hope for patients with advanced SCC.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest

D.R. Gandara reports receiving speakers bureau honoraria from Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, Genentech, Merck, Novartis, and Synta Pharmaceuticals. P.S. Hammerman is a consultant/advisory board member for ARIAD Pharmaceuticals, AstraZeneca, Clovis Oncology, ImClone Systems, Janssen, and MolecularMD. M.L. Sos is a consultant/advisory board member for Blackfield. P.N. Lara Jr is a consultant/advisory board member for Lilly Oncology. F.R. Hirsch is a consultant/advisory board member for AstraZeneca, Bristol-Myers Squibb, Genentech, ImClone Systems/Eli Lilly, Novartis, and Pfizer. No other potential conflicts of interest were disclosed.

Figures

Figure 1
Figure 1
Schematic overview of potential modulators of cellular response to FGFR targeted drugs in FGFR1-amplified lung SCC. It has been shown that the chromosomal architecture of the 8p12 locus as well as the expression of c-MYC can modify (gray arrows) the cellular dependency on FGFR1 and therefore the efficacy of FGFR inhibitors in these tumors. Similarly, the secretion (black arrows) of FGF ligands (e.g. FGF2, FGF9) can perturb the activity of FGFR1 and modify the response to targeted inhibition of its kinase activity.
Figure 2
Figure 2
Venn diagram for degree of overlap of 158 candidate prognostic genes. Reference sources are shown. Reprinted from Lau et al. (29).
Figure 3
Figure 3
Aims and research approach for the Squamous Lung Cancer SPECS Consortium.
Figure 4
Figure 4
A, Overall schema for Lung-MAP and B, the initial drug classes being tested, PI3K, FGFR, CDK 4/6, HGF and PD-L1. TT=Targeted therapy, CT=chemotherapy (docetaxel or gemcitabine), E=erlotinib
Figure 4
Figure 4
A, Overall schema for Lung-MAP and B, the initial drug classes being tested, PI3K, FGFR, CDK 4/6, HGF and PD-L1. TT=Targeted therapy, CT=chemotherapy (docetaxel or gemcitabine), E=erlotinib
See this image and copyright information in PMC

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