New Delhi: Lung cancer is a leading cause of cancer mortality globally, with recurrence and metastasis remaining significant challenges. Recent advances in liquid biopsy technology are transforming how clinicians detect and manage lung cancer progression. By analyzing biomarkers in blood and other body fluids, liquid biopsies offer a minimally invasive alternative to traditional tissue biopsies, enabling dynamic monitoring of cancer’s molecular landscape. This is particularly valuable for identifying resistance mechanisms, predicting treatment outcomes, and detecting recurrence or metastasis, especially in cases when the tumor tissue is insufficient or inaccessible for genomic profiling.
Dr. Urvashi Bahadur, VP of clinical Genomics and Senior Director of medical Genetics and Genomics, at Strand Life Sciences, while interacting with News9Live, explained how liquid biopsies work and what their benefits are.
Biomarkers Detected Through Liquid Biopsy
Liquid biopsies primarily analyze circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and other molecular fragments released by tumors into the bloodstream. Key biomarkers in NSCLC include:
- EGFR Mutations: Liquid biopsy is especially effective in detecting actionable mutations like EGFR L858R, exon 19 indels or resistance mutations such as T790M, the latter often emerges in response to tyrosine kinase inhibitor (TKI) therapy. Studies have demonstrated high sensitivity in ctDNA analysis for identifying T790M-mediated resistance, guiding the use of third-generation EGFR inhibitors like osimertinib.
- MET Amplifications: MET amplifications, a frequent bypass mechanism, can also be detected using liquid biopsies. Emerging assays help identify MET-driven resistance to EGFR-targeted therapies and monitor tumor evolution during treatment. Patients with MET amplifications can be placed on MET inhibitors.
- RET Rearrangements: RET rearrangements are increasingly being recognised as actionable targets in lung cancer. Liquid biopsy enables the detection of these rearrangements, indicating the use of RET inhibitors like pralsetinib and selpercatinib. This is particularly valuable in cases where tissue biopsies fail to yield conclusive results.
- ALK Rearrangements: Anaplastic lymphoma kinase (ALK) rearrangements, such as ALK-EML4 fusions, drive tumor progression in a subset of lung cancers. Liquid biopsy can identify these rearrangements, which are associated with high sensitivity to ALK inhibitors like alectinib and lorlatinib. It also enables monitoring for secondary mutations in ALK that confer resistance to first-line therapies.
- KRAS Mutations: Liquid biopsies reliably detect KRAS mutations, such as KRAS G12C, which is gaining importance due to the development of new targeted therapies like sotorasib and adagrasib. Tracking these mutations in ctDNA can offer insights into treatment response and early resistance.
- STK11 and KEAP1 Mutations: These mutations are increasingly being identified and are associated with poor responses to immunotherapy. Their detection via liquid biopsy can provide critical prognostic information, particularly for metastatic cases.
Managing Recurrence and Metastasis with Liquid Biopsy
Liquid biopsies enable early detection of molecular residual disease (MRD), a state where traces of ctDNA remain post-treatment. Studies show that rising ctDNA levels can predict recurrence months before clinical symptoms or imaging findings. This allows oncologists to tailor surveillance strategies and initiate treatment early.
For metastatic lung cancer, liquid biopsy facilitates real-time monitoring of disease progression. Monitoring disease progression is useful because it helps identify new emergent mutations that arise in response to a particular treatment regimen and the identification of such mutations informs clinicians about resistance. For example, MET amplification is a frequently observed acquired resistance mechanism and its presence indicates a need to switch to MET inhibitors.
Liquid biopsies offer numerous advantages, including reduced invasiveness, real-time tumor monitoring, and the ability to detect tumor heterogeneity. Advanced platforms, such as the Somatic Advantage 74 Liquid Biopsy Test from Strand, now integrate multiple genes, enabling the simultaneous detection of multiple biomarkers.
Liquid biopsy represents a paradigm shift in managing lung cancer recurrence and metastasis. By identifying and monitoring key biomarkers like EGFR, MET, KRAS, STK11, and KEAP1 mutations, this technology enables oncologists to tailor treatment strategies dynamically. As liquid biopsy technologies continue to evolve, their integration into clinical practice holds the promise of improving survival and quality of life for lung cancer patients.
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