How Genetics Is Changing Everything We Know About Lung Cancer?

A 46-year-old man was diagnosed with pleural effusion - a case of fluid accumulation around the lungs. According to his diagnostic tests, he was a confirmed case of stage 4 adenocarcinoma of the lung - a particularly advanced and aggressive lung cancer. However, instead of immediately beginning broad-spectrum chemotherapy, his oncologist sent a tissue sample for Next Generation Sequencing or NGS, where results revealed a rare PRKAR1A::ALK fusion, a genetic abnormality that was driving the cancer's growth. “Using this information, his doctors began Lorlatinib therapy. This is a targeted drug that specifically blocks the ALK fusion protein. The outcome was extraordinary: after eight months, scans showed no detectable disease, and follow-up imaging

in March 2024 confirmed complete remission with no active lesions,” Dr Prashanth Bagali, Head of Scientific Affairs, MedGenome, told Times Now.

What is an NGS test?

NGS testing is a modern laboratory technique that rapidly sequences millions of DNA or RNA fragments at the same time to analyze genetic information. This high-throughput method allows for the comprehensive analysis of entire genomes, large DNA segments, or specific genes, and is used for disease diagnosis, monitoring treatment response, and personalized medicine. Unlike older, single-strand methods, NGS provides massive parallel sequencing for faster and more comprehensive genetic analysis. “The NGS test was successfully used in this clinical case to achieve a complete response. The case exemplifies the impact of genomic testing in shaping treatment decisions. A single molecular insight completely reshaped the treatment plan and outcome, turning what was once a terminal diagnosis into a successful recovery,” said Dr Bagali. In India, Lung cancer continues to be among the most aggressive and fatal cancers. A 2025 report from the National Institutes of Health - nearly 5.9 per cent of all cancers and 8.1 per cent of all cancer-related deaths in the country are caused by lung cancer. What makes this particularly concerning is that most cases are detected only after the disease has advanced.

The genetic dimension

Over the past few years, our understanding of lung cancer has significantly advanced. In addition to lifestyle and environmental factors, genetic mutations are now identified as primary causes of the disease. Gene alterations such as EGFR, ALK, ROS1, and KRAS can trigger and cause lung cells to multiply uncontrollably. While the majority of lung cases, about 90 to 95 per cent, are caused by acquired or spontaneous genetic mutations resulting from environmental and lifestyle factors like smoking, a smaller portion, around 5 to 10 per cent, is linked to inherited factors. Genetic testing can be revealing for individuals who have a family history of inherited lung diseases, which can increase lung cancer risks, such as Chronic Obstructive Pulmonary Disease and lung cysts. Inherited syndromes like Li-Fraumeni syndrome, caused by TP53 gene mutations, are associated with an increased risk for lung cancer. Examining the genetic makeup of a patient’s tumour helps clinicians spot the exact mutations and molecular changes that influence disease progression and response to treatment.

Precision medicine in action

Genetic testing has transformed how lung cancer is treated, shifting healthcare from one-size-fits-all to a highly targeted, personalized approach. “Just by decoding the tumor's genetic profile, doctors can personalize therapy plans. For example, patients with EGFR mutations may receive one type of targeted inhibitor, while those with ALK or ROS1 fusions may exhibit better response to other precision treatments,” added Dr Bagali. These therapies are more precise, usually causing fewer side effects than conventional chemotherapy. As a result, we're now witnessing patients living longer, with better quality of life, as treatment decisions are guided by the tumor's genetic profile and pathological behavior rather than just its location.

What is the way forward?

India's rising lung cancer numbers call for a shift in how we approach diagnosis and treatment. It is vital to spread awareness that lung cancer can occur in non-smokers as well. Conducting genetic tests at an early stage should be standardized in clinical practice, especially for patients with advanced disease or for those who develop lung cancer without smoking. This Lung Cancer Awareness Month, it is important to understand and recognise that both genetic and environmental factors can lead to lung cancer. Timely screening and intervention enable more effective therapy, fewer side effects, and higher chances of remission, even in advanced disease. Making genomics a standard part of cancer care offers not only better outcomes but also a significant change in what is possible for lung cancer patients in India.