Indian study finds what makes thyroid cancer aggressive, recurrent and treatment-resistant: What this means for precision therapy
Published in 'JCO Global Oncology,' the research is spearheaded by graduate student Vaishakhi Trivedi under the mentorship of Dr Kumar Prabhash and Dr Amit Dutt. 'Our work not only adds data to global cancer databases —it also redefines what is known about thyroid cancer in the Indian population,' Dr Dutt said.
The rogue gene in the most common thyroid cancer
The study concerns papillary thyroid cancer (PTC), which accounts for 80-85 per cent of all thyroid cancer cases in India. This is considered treatable. The team analysed DNA from 100 Indian patients and found mutations in the DUOX2 gene found in nearly nine per cent of cases. 'This gene, previously known for its role in thyroid hormone production, now appears to be a genetic red flag for recurrence and poor prognosis. This is the first time DUOX2 has been implicated as a predisposing factor in PTC. It offers an opportunity for early detection and potentially life-saving interventions,' Dr Dutt said.
Study uncovers two distinct molecular subtypes
The study even identified two different subtypes associated with aggressive cancer and high recurrence. The BRAF-RAS-driven subtype makes up 62 per cent of cases and is identified by mutations that are often tied to more aggressive tumour behaviour. The iBR (Independent of BRAF-RAS) subtype is a newly-defined category. 'This group lacks traditional mutations but shows alarming signs of treatment resistance and high recurrence. It is marked by alterations in genes like SMAD4 and TG — a previously uncharted territory for thyroid oncologists,' said Dr Dutt.
This dual classification signals a new era of care where treatments are tailored to the patient's genetic profile rather than a one-size-fits-all approach.
Cracking the genetic code of an aggressive form of thyroid cancer
While PTC is common and often curable, anaplastic thyroid cancer (ATC) is its deadly cousin — rare, fast-moving and resistant to nearly every treatment in the book. The research team examined 68 samples and found mutations in the THRA gene in 11 per cent of Indian patients. This is in sharp contrast to Caucasian datasets.
'THRA, a gene tied to thyroid hormone signalling, appears to be a key player in cellular plasticity or the process by which cancer cells morph, lose their identity and become more aggressive. THRA mutations are like flipping the switch. They make the cancer harder to kill but they also give us a target. That's a rare silver lining,' Dr Prabhash explained.
What this means for Indian patients — and the world
These findings offer practical methods of how thyroid cancers are diagnosed, treated and managed in Indian patients. 'Patients with DUOX2 mutations could be monitored proactively, much like BRCA testing in breast cancer. This may help in diagnosing aggressive PTC early and prevent a relapse,' Dr Dutt said. Researchers also added that therapies that restore THRA function may finally give ATC patients a fighting chance.
'We need a personalised roadmap for thyroid cancer. With the promise of advanced tools like CRISPR gene editing and small-molecule inhibitors, these discoveries could soon migrate from the lab bench to the bedside,' the researchers said. 'Genetic profiling should be as routine as a biopsy,' said Vaishakhi Trivedi. 'We have the science. Now we need the systems to support it.'
Anuradha Mascarenhas is a journalist with The Indian Express and is based in Pune. A senior editor, Anuradha writes on health, research developments in the field of science and environment and takes keen interest in covering women's issues. With a career spanning over 25 years, Anuradha has also led teams and often coordinated the edition.
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