Modern cancer medicine increasingly relies on tumor DNA profiling and next-generation sequencing to refine diagnoses, guide targeted treatments, and monitor disease progression through liquid biopsies. While technologies like tissue-agnostic approvals and circulating tumor DNA analysis offer new hope, challenges such as high costs, interpretation complexities, and underrepresented regional genomic data remain significant hurdles. Expanding local databases, like the Indian Cancer Genome Atlas, and improving affordability are crucial steps toward making precision oncology accessible to more patients.

Modern cancer medicine increasingly relies on tumor DNA profiling and next-generation sequencing to refine diagnoses, guide targeted treatments, and monitor disease progression through liquid biopsies. While technologies like tissue-agnostic approvals and circulating tumor DNA analysis offer new hope, challenges such as high costs, interpretation complexities, and underrepresented regional genomic data remain significant hurdles. Expanding local databases, like the Indian Cancer Genome Atlas, and improving affordability are crucial steps toward making precision oncology accessible to more patients.

Modern cancer medicine increasingly relies on tumor DNA profiling and next-generation sequencing to refine diagnoses, guide targeted treatments, and monitor disease progression through liquid biopsies. While technologies like tissue-agnostic approvals and circulating tumor DNA analysis offer new hope, challenges such as high costs, interpretation complexities, and underrepresented regional genomic data remain significant hurdles. Expanding local databases, like the Indian Cancer Genome Atlas, and improving affordability are crucial steps toward making precision oncology accessible to more patients.

For most of modern medicine, a cancer was known by the organ where it began. Today, doctors increasingly ask a second question: what has gone wrong inside the tumour's DNA? Cancer arises through accumulated changes in a cell's genes, and this molecular profile can refine diagnosis, predict treatment response and inform prognosis. Histopathology remains the foundation of diagnosis, but in some tumours, such as adult diffuse gliomas, genetic findings are now part of the diagnosis itself.

Laboratories once tested for one genetic change at a time. Next-generation sequencing now allows a single panel to detect point mutations, small insertions and deletions, copy-number changes and, with RNA testing, gene fusions. It can also measure tumour mutational burden and microsatellite instability, which help identify candidates for immunotherapy. This matters when a biopsy is small, because sequential single-gene tests can exhaust the tissue. Lung cancer remains the model, with alterations in EGFR, ALK, ROS1, BRAF and RET directing patients to targeted therapies.

Some treatments now follow the biomarker rather than the organ. By late 2025, the US Food and Drug Administration had granted nine "tissue-agnostic" approvals across six biomarkers, including NTRK fusions, BRAF V600E mutations and microsatellite instability. For some patients with rare tumours, this has opened options that once did not exist.

Tumours shed fragments of DNA into the bloodstream, known as circulating tumour DNA (ctDNA), and a liquid biopsy detects them in a blood sample. In advanced cancer, it can identify therapeutic targets when tissue is hard to obtain and reveal resistance mutations emerging during treatment. After curative surgery, it may detect molecular residual disease before scans can.

Colon cancer shows both the promise and the limits. In the randomised DYNAMIC trial in stage II disease, ctDNA-guided management reduced adjuvant chemotherapy from 27.9% of patients to 15.3%, with five-year recurrence-free survival of 88% versus 87%. Escalation has been less rewarding: in the DYNAMIC-III trial, intensified chemotherapy did not improve recurrence-free survival in ctDNA-positive stage III patients. Predicting relapse is not the same as preventing it. A negative test does not guarantee a cure either, because low-shedding peritoneal and lung recurrences can be missed.

The need in India is substantial. The National Cancer Registry Programme projected about 15.6 lakh new cancer cases and 8.7 lakh cancer deaths for 2024. Local genomic data matter too: a meta-analysis of Indian patients with advanced non-small cell lung cancer reported EGFR mutations in about 24% of cases and 29% of adenocarcinomas, with ALK rearrangements in about 8% of adenocarcinomas.

Indian genomes have been underrepresented in global reference databases, which can make rare variants harder to interpret. GenomeIndia analysed the genomes of 9,768 healthy people from 83 populations and found 44 million variants absent from major global databases. The Indian Cancer Genome Atlas has also begun sharing open multi-omics data from Indian breast cancer patients. Access, however, remains uneven: cost keeps comprehensive genomic profiling out of reach for many Indian patients, although targeted sequencing panels offer a more affordable route.

A genomic report is not a ready-made prescription. Many variants are benign, of uncertain significance or have no matching drug, so each result must be weighed against tumour content, variant allele fraction, assay limits and the clinical evidence. Tumour sequencing may also suggest a germline variant, for example in BRCA1 or BRCA2, which matters for relatives and calls for confirmatory testing and genetic counselling. In blood tests, clonal haematopoiesis can mimic tumour-derived mutations.

Expectations must also remain realistic. A US estimate for 2018 put eligibility for genome-targeted therapy at about 8% of patients with advanced cancer, with about 5% likely to benefit. Those figures are dated, but the lesson holds: a genomic profile does not guarantee a matched drug, a response or affordable access.

The next task is to make these tools affordable and to build stronger evidence from Indian patients. The field is now moving towards integrating DNA findings with transcriptomic, methylation and clinical data. Its real value lies in bringing the right test to the right patient at the right time, with a report the care team can act on. Cancer remains a complex opponent, but we are learning to read it far more clearly.

The author is the chairman and joint managing director of Suraksha Diagnostic Limited, a listed entity. A physician-turned-diagnostics entrepreneur, he also heads Suraksha Institute of Genomics.

 

The opinions expressed in this article are those of the author and do not purport to reflect the opinions or views of THE WEEK.

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