Squamous Cell Lung Cancer: Where Do We Stand and Where Are We Going?

Over the last decade much progress has been achieved in non–small cell lung cancer (NSCLC) in terms of knowledge and treatment opportunities, but these advances have largely been made in management of patients with the adenocarcinoma subtype. In the paradigm shift toward personalized medicine based on therapies targeting “oncogenic drivers,” lung cancer has emerged as a shining example of the benefit of modern cancer therapy (eg, through targeting of epidermal growth factor receptor [EGFR] gene mutations, ALK gene rearrangement). However, improvements have not occurred in the treatment of patients with squamous cell lung cancer (SqCC) subtype of NSCLC, which represents 25% to 30% of all lung cancers and accounts for 60,000 to 70,000 new lung cancer diagnoses and about 50,000 deaths annually in the United States. Patients with SqCC are still stigmatized; these patients tend to be (heavy) smokers and are often elderly compared with adenocarcinoma patients. Investigation of SqCC is severely underfunded, and encouraging therapeutic progress is lacking. Fortunately, however, this stigma has recently begun to lift, mainly as a result of data resulting from the efforts of The Cancer Genome Atlas (TCGA) project, from which selected findings relevant to SqCC are presented and discussed in the current issue of ONCOLOGY by Dr. Devarakonda and colleagues.[1] While the authors nicely describe current clinical applications of TCGA results to the treatment of SqCC, much work remains to be done to improve clinical outcomes for this group of patients. Fortunately, several recently launched initiatives are directed toward meeting the therapeutic needs of patients with SqCC; an important new initiative is The Squamous Lung Cancer Consortium (SLCC), a research network of eight academic institutions in the US and Canada. The main goal of the SLCC is to stimulate research that will improve the management of SqCC. The National Cancer Institute (NCI) is currently supporting SLCC efforts to evaluate different prognostic signatures with the goal of developing a standardized molecular prognostic classifier, under the NCI SPECS (Special Program Evaluating Cancer Signatures) grant. This SLCC project also is validating TCGA findings and studying their prognostic implications for treatment of SqCC. Another large clinical initiative in SqCC is the development of clinical “Masterprotocols” for patients with SqCC, based on an annual molecular screening of 500 to 1,000 patients with SqCC for defined “molecular drivers” with therapeutic trials linked to the genetic abnormalities/oncogenic drivers. The latter initiative is a collaboration between the NCI, the US Food and Drug Administration (FDA), and the organization Friends of Cancer Research (www.focr.org). The “Masterprotocol” is a specifically designed biomarker-driven clinical trial protocol, the goal of which is to quickly identify new active drugs against SqCC, and which, through the developed appropriate trial design, eventually could lead to rapid FDA approval and registration for any identified active drug against SqCC.

The results from TCGA are valuable not only from a therapeutic perspective, but also from the perspective of diagnosis and early detection. In the large randomized US National Lung Screening Trial (NLST), lung cancer screening with low-dose CT has demonstrated a 20% reduction in lung cancer mortality, compared to conventional chest x-ray screening. However, more than 90% of the screen-detected nodules were “false positive,” which means that other methods of determining whether a nodule is benign or malignant need to be developed.[2] In other words, a good “biomarker” test adjunctive to the imaging process could be of significant value in the setting of screening. TCGA data give us knowledge about the biology of SqCC, as well as some biomarker leads to consider in developing such a test. Eventually these data may provide clues to potential chemoprevention measures as well, although tobacco prevention/cessation efforts will still be the most relevant approaches in this particular group of patients.

Thus, while TCGA results have led to some encouraging advances in the clinical perspective on SqCC, as nicely presented in the article by Dr. Devarakonda and colleagues, this initiative has already spurred many other new initiatives targeting patients with SqCC. This gives us hope for future improvements in clinical management and therapeutic outcomes for this subgroup of lung cancer patients.

Financial Disclosure:The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

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REFERENCES

1. Devarakonda S, Morgensztern D, Govindan R. Clinical applications of TCGA for squamous cell carcinoma. Oncology (Williston Park). 2013;27:899-915.

2. National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, et al. Reduced lung cancer mortality with low-dose computed tomography screening. N Engl J Med. 2011;365:395-409.