Overall, “the genomic profile seen in the 26 patients with lung SCC is similar to the previously reported in studies carried out in North American and Asian cohorts,” Cardona et al said.
Though the genetic profile of the Colombian patients resembled those of North American and East Asian individuals with lung SCC, the populations were characterized by several differences. For example, in Cardona et al’s study, nearly all patients (96%) had advanced disease, but in the North American and Korean cohorts, approximately 40% and 20% of patients were diagnosed with advanced disease, respectively. These differences could explain certain variations in mutagenic profile between studies, such as the higher mutation rates seen for MLL2, KEAP1, NF1, PIK3CA, STK11, and TP53, and the lower mutation rates noted for STK11, PTEN, KRAS, HRAS, and SOX2 in Cardona et al’s evaluation.
Although there is high unmet need for new targets and tailored treatments in the lung SCC setting, Cardona et al’s findings could help underscore potential new targets and ways of classifying patients, according to Raphael Bueno, MD, chief of the division of thoracic surgery at Brigham and Women’s Hospital in Boston, Massachusetts. “We’ve been catching up on adenocarcinoma, but in squamous, it’s [been] unchanged for the past 30 years.”
Existing evidence on mutation burden and prevalence has fueled efforts to tailor treatments for lung adenocarcinoma, but research into the genomic characteristics of lung SCC has been scarce, leading to a paucity of targeted therapies for the disease, which accounts for approximately 85,000 new cases in the United States annually, and more than 400,000 globally.
Although the data from Cardona et al’s analysis refine available insight on the genomic landscape of lung SCC, the mutations identified in the study have already been reported in other equivalent evaluations and do not constitute breakthrough discoveries, according to Fred R. Hirsch, MD, PhD, executive director of the Center for Thoracic Oncology in The Tisch Cancer Institute at Mount Sinai in New York, New York. “This study might be interesting, but it doesn’t bring anything new,” Hirsch said.
Nevertheless, “papers like this illustrate the complex interactions between the tumor genomic alterations and tumor microenvironment,” said Ramaswamy Govindan, MD, director of the Section of Medical Oncology at Washington University School of Medicine in St. Louis, Missouri. Akin to prior research, the findings from Cardona et al’s study suggests that certain tumor genomic alterations may affect the expression of PD-L1, he said.
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