Identification of Lung Cancer Subtypes May Lead to Better, Tailored Therapies

Identification of Lung Cancer Subtypes May Lead to Better, Tailored Therapies

An analysis of more than 1,000 non-small cell lung cancers (NSCLC) has shown that this type of cancer can be divided into nine different subtypes according to its gene expression patterns, a finding that may enhance tailored therapies for patients with this cancer.

The study, “Multiplatform-based molecular subtypes of non-small-cell lung cancer,” was published in Oncogene, and conducted by researchers at the Baylor College of Medicine and the University of Texas MD Anderson Cancer Center.

“People may think of lung cancer as one disease, but lung cancer is a collection of diverse subtypes of cells and each subtype may respond differently to the same therapy,” senior author Chad Creighton, PhD, associate professor of medicine and member of the Dan L Duncan Comprehensive Cancer Center Division of Biostatistics at Baylor College of Medicine, said in a press release.

The two predominant NSCLC histological subtypes are adenocarcinoma and squamous cell carcinoma, which were recently profiled at the molecular level by The Cancer Genome Atlas (TCGA), uncovering the molecular basis of each subtype of NSCLC.

The researchers used the most recent data included in TCGA lung data sets, analysing the molecular data of more than 1,000 NSCLC cases. This data included information regarding the genes and proteins expressed in cancer cells, for example, as well as epigenetic changes in these cells, which allowed them to identify distinct subtypes of NSCLC — three within squamous cell carcinomas, and six within adenocarcinomas.

“Any two given lung cancers may have very different molecular profiles,” said Creighton. “One would have certain genes turned on and produce certain proteins while the other cancer would have different genes turned on and express different proteins. This would imply that one cancer subtype might be more vulnerable to specific therapies while the other might be more susceptible to other therapies,” he said.

Indeed, the researchers found specific NSCLC subsets that are more likely to respond to immunotherapies, as they express several immune checkpoint genes, including PD-L1 and PD-L2, and are widely infiltrated by immune cells.

“One big part of the study was to try to tease out the cells in the tumor that actually are not cancer,” said Creighton. “Those cells include lymphocytes — a type of immune cell that tries to attack the cancer. Lymphocytes showed up in the tumor profile and we found out that only specific subsets of lung cancer show this really strong pattern for lymphocyte infiltration. These cancer subtypes also show evidence for immune checkpoint pathway, which is a pathway by which cancer cells learn to evade the immune system, which normally would actively attack and kill cancer cells. Many cancers have learned some ‘tricks’ so they can turn on or off specific genes or proteins that allow them to evade the immune response,” he said.

Now researchers are planning to identify genetic subtypes in a number of other cancers, providing further insights on possible therapies that might work in each specific subset.

“The Cancer Genome Atlas, the cancer initiative that generated these data that we analyzed, involves data for over 10,000 cancers,” said Creighton. “That information is now in the public domain and we are currently going through all of the data, not just for lung cancer, but for all the cancer types. We call this pan cancer analysis. We are trying to find features that not just apply to one type of cancer, but across multiple types. Much of our work in the next year is going to be focusing on pan cancer work that might point at ways of treating multiple types of cancer,” he said.

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