Lung cancer remains one of the most prevalent and deadly cancers globally, with approximately 2.2 million new cases diagnosed annually, contributing to 18 per cent of all cancer-related deaths, according to the International Agency for Research on Cancer. In India, it continues to be a leading cause of cancer-related mortality. However, advancements in early detection and new treatment options, particularly genetic profiling, are improving survival rates. These innovations are part of precision oncology, a rapidly growing field that customises treatments based on a patient’s unique genetic makeup, enabling personalised care.
In observance of lung cancer awareness month this November, Metropolis Healthcare conducted a landmark seven-year research study (2015-2021) to examine the clinicopathological features and molecular changes in lung cancer patients. The study analysed data from over 3,200 individuals diagnosed with lung cancer, focusing on genetic alterations in key genes such as Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK), and c-ros oncogene 1 (ROS1). These genes play a pivotal role in the development of non-small cell lung cancer (NSCLC). Molecular markers like these are essential for guiding targeted therapies, which are revolutionising lung cancer care by tailoring treatment to each patient’s genetic profile.
Key Findings of the Study:
More than 3,200 lung cancer tissue samples were analysed, with 83 per cent diagnosed as adenocarcinoma (a common type of NSCLC) and 17 per cent as squamous cell carcinoma (a subtype affecting the lung’s airways). Both types were most common in patients over 60 years.
The most common genetic alterations found were:
- EGFR mutations (29.1 per cent) – Mutations in the Epidermal Growth Factor Receptor (EGFR) gene, which are common in lung cancer and make the patient a candidate for targeted treatment.
- ALK rearrangements (7.8 per cent) – Changes in the Anaplastic Lymphoma Kinase (ALK) gene are also a target for treatment.
- ROS1 rearrangements (3.5 per cent) – Alterations in the ROS1 gene, which, like ALK, can also fuel cancer progression & are amenable to targeted therapy.
- EGFR Mutation Locations: EGFR mutations were most commonly found in exon 19 (65.6 per cent) and exon 21 (32.1 per cent). These are specific regions of the EGFR gene where changes can affect its function, often leading to uncontrolled cell growth.
- Higher rates of EGFR mutations were observed in younger patients, and they were more frequent in female patients.
- ALK positivity was more frequently detected in younger patients, with a balanced gender distribution.
Impact:
- Molecular markers like EGFR mutations, ALK, and ROS1 rearrangements are key targets for treatment in NSCLC, with approved drugs available for these alterations.
- Next-generation sequencing (NGS) helps identify more lung cancer cases and uncover additional molecular targets, leading to more treatment options.
Commenting on the study, Dr Kirti Chadha, Chief Scientific and Innovation Officer and Senior Oncopathologist, Metropolis Healthcare, said, “Studying genetic mutations and alterations in cancer-related genes is essential for guiding clinicians in selecting the most suitable treatment—whether it involves surgery, medications, or chemotherapy. This detailed molecular analysis forms the foundation of personalised and precision medicine, allowing doctors to adjust therapies based on a patient’s unique genetic profile and likely response. By tailoring treatments in this way, clinicians can significantly improve the effectiveness of NSCLC cancer care, offering patients treatment approaches best aligned with their individual needs.”
The study underscores the importance of molecular profiling in NSCLC, as identifying these genetic alterations can guide targeted therapy, potentially improving patient outcomes. Advances in molecular diagnostics, particularly Next Generation Sequencing (NGS), have revolutionised the field of oncology. NGS allows for the simultaneous sequencing of multiple genes, providing comprehensive insights into the genetic makeup of tumours. This technology enables the identification of actionable mutations, helping oncologists tailor treatments to individual patients.
The 2017 NCCN guidelines highlighted the importance of genetic profiling in NSCLC, focusing on key mutations in ALK, ROS1, and EGFR. Building on this, the 2023 ESMO guidelines for metastatic NSCLC emphasised a broader set of biomarkers, including BRAF, RET, MET, NTRK, HER2, and KRAS G12C, using advanced DNA and RNA panels. This underscores the critical role of molecular diagnostics in decoding lung cancer’s genetic landscape to enable personalised treatment strategies.