Biomarkers in Non-Small Cell Lung Cancer

Biomarkers in non-small lung cancer is a substance or molecule in the body which shows presence of cancer in the body. These biomarkers may be a protein or molecule occurred by a tumor or a specific gene type which is related to a cancer.These biomarkers help doctors with the diagnosis of a cancer and how to treat it.

Biomarkers in non-small lung cancer can be detected by “biomarker testing”. Indicator molecules can be measured by blood, body fluids or tissue. According to molecular signs of health, doctors can plan the treatment. Targeted therapy can be used to control and suppress these molecules. For non-small cell lung cancer, there are some therapies for specific gene types.

What are Biomarkers in Non-small Cell Lung Cancer?

Traditionally non-small cell lung cancer has been treated with systemic chemotherapy, which are often cytotoxic. However, a paradigm shift emerged in the early 2000’s with the discovery of genomic alterations that predict responses to targeted therapy, particularly in lung adenocarcinoma, a subtype of non-small cell lung cancer. Currently, clinically actionable genomic abnormalities with FDA approved drugs include alterations in the following genes – EGFR, ALK, ROS1, MET, RET, NTRK1/2/3, and BRAF. Most of these mutations are acquired in a patient’s lifetime (somatic) and occur exclusively in cancer cells. Incidentally, the targeted therapies for MET and RET genes were approved for the first time in 2020 demonstrating the ever-evolving landscape in precision oncology. As such, the presence of multiple alterations that have targeted therapy in lung cancer, underscores the importance of genetic testing.

Biomarkers for Non-Small Cell Lung Cancer

EGFR mutations: The discovery of mutations in the epidermal growth factor receptor (EGFR) that were sensitive to tyrosine kinase inhibitors heralded the advent of precision medicine for non-small cell cancer. Oncogenic mutations in EGFR are found in approximately 12% of lung adenocarcinoma patients. In general EGFR mutations are more common in patients with no prior history of smoking and in females. Many of these EGFR mutations activate molecular pathways that promote cancer cell survival, increased cell proliferation and tumor cell motility. The FDA has approved multiple EGFR inhibitors for lung cancer patients with EGFR mutations including erlotinib, gefitinib, afatinib, osimertinib and dacomitinib. These drugs in general slowdown the cancer growth by negating the effect of EGFR mutations. In a clinical trial, the progression free survival of lung cancer patients on Osimertinib was found to be 19 months in comparison to 10 months with standard chemotherapy.

ALK fusions: Gene fusions (rearrangements) with the anaplastic lymphoma kinase (ALK) gene is detected in approximately 3-5% of lung adenocarcinoma patients. When the ALK gene fuses with another gene EML4, that event can trigger development of lung cancer by activating oncogenic pathways. Typically, ALK fusions are more commonly seen in younger patients and non/light smokers. ALK fusions have been traditionally detected by a technique call fluorescent in-situ hybridization (FISH); however, there is increasing use of next generation sequencing approaches to detect these fusions. The FDA has approved multiple ALK inhibitors for lung cancer patients with ALK fusions including crizotinib, ceretinib, alectinib, lorlatinib, and brigatinib. ALK fusions are typically not found in patients with EGFR mutations.

ROS1 fusions: ROS1 fusions occur approximately in 1-2% of lung adenocarcinoma patients and are generally identified in younger non-smokers. ROS1 can partner with numerous other genes to create an oncogenic fusion that may lead to lung cancer. The FDA has approved crizotinib and entrectinib for metastatic lung adenocarcinoma patients with ROS1 fusions. While ROS1 fusions are rare in lung cancer, it is important to test for this biomarker as a positive result will open targeted treatment options.
MET alterations: The MET gene can be altered in lung adenocarcinoma either by the presence of extra copies of the gene or by a mutation called exon 14 skipping that makes the gene shorter. MET alterations are found in approximately 5% of lung cancer patients. These alterations in MET leads to increased cell proliferation and invasion causing cancer. The FDA has approved capmatinib in May 2020 for lung adenocarcinoma patients with MET exon 14 mutations availing an approved targeted treatment option for the first time in this sub-group of patients.

RET fusions: Similar to ALK and ROS1 fusions in lung adenocarcinoma, RET fusions can initiate and drive the tumor. RET fusions have been reported in approximate 1-2% of lung adenocarcinoma patients. The FDA has approved selpercatinib for lung cancer patients with RET fusions. In the clinical trial that evaluated this drug, over 80% of the patients derived clinical benefit for 6 months or longer.

NTRK fusions: Fusions in NTRK1, NTRK2, and NTRK3 have been identified in various cancer types including lung adenocarcinoma. NTRK fusions can send cellular signals to trigger unregulated cell growth in many different cancers. The FDA has approved larotrectinib and entrectinib for all solid tumors with NTRK fusions agnostic of the cancer type.
BRAF mutations: While BRAF mutations are commonly associated with melanoma and thyroid cancer, they are also present in approximately 7% of lung adenocarcinoma patients. BRAF mutations, in particular the V600E mutation mediates tumorigenesis by activating cancer forming molecular pathways. The FDA has approved dabrafenib and trametinib combination drug therapy for non-small cell lung cancer patients with BRAF V600E mutations.

Non-small Cell Lung Cancer Clinical Trials

Research studies are ongoing for finding new ways to provide better treatment for NSCLC patients. Patients who do not respond to current treatment options may consider clinical trials. Massive Bio allows you to come together with clinics and researchers who research your specific disease. For more information about non-small cell lung cancer clinical trials, you can contact Massive Bio.