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The Mother's Legacy: A Hidden Gene That Shields Deadly Melanoma from Cures

James Thomas•Jun 5, 2025
A stylized image of a human silhouette with a glowing mitochondrial DNA strand prominently displayed, where a specific segment (representing HG-T) is highlighted in a contrasting color, symbolizing its critical impact on treatment response.
  • A newly identified genetic trait, passed down from mother to child, significantly predicts resistance to life-saving immunotherapy in metastatic melanoma patients.
  • Patients with the mitochondrial haplogroup T (HG-T) mutation are nearly 3.5 times less likely to respond to common checkpoint inhibitor treatments.
  • This groundbreaking discovery by NYU Langone Health researchers could revolutionize treatment, allowing doctors to identify resistant patients early and explore alternative therapies.

For years, a heartbreaking mystery has plagued cancer treatment: why do powerful immunotherapies, heralded as a revolution in fighting metastatic melanoma, fail nearly half of the patients who desperately need them6, 8? Now, a landmark study offers a startling answer, tracing the resistance back to a genetic signature hidden within our cells' powerhouses—the mitochondria.

Metastatic melanoma, a relentless killer claiming nearly 10,000 American lives annually, often meets its match in checkpoint inhibitors. These drugs unmask cancer cells for destruction by the immune system. Yet, for many, this promise of healing remains unfulfilled. Researchers at NYU Langone Health and its Perlmutter Cancer Center, analyzing 1,225 patients in a global trial, pinpointed an inherited trait, mitochondrial haplogroup T (HG-T), as a key saboteur6. Their findings, published with DOI: 10.1038/s41591-025-03699-3, reveal that individuals carrying this maternally-inherited mutation are 3.46 times less likely to benefit from these crucial therapies.

Mitochondrial DNA, uniquely passed from mother to offspring, carries this HG-T variant. The study suggests HG-T may stunt the development of vital T-cells, the immune system's soldiers, rendering them less effective against the cancer. This discovery, validated in a separate patient group, opens the door to predictive testing, sparing resistant patients ineffective treatments and guiding them towards potentially life-saving alternatives sooner, transforming the fight against this deadly disease6, 8.

References

  1. med.nyu.edu
  2. nyulangone.org
  3. clinicaltrials.med.nyu.edu
  4. nyulangone.org
  5. nyulangone.org
  6. www.prnewswire.com
  7. nyulangone.org
  8. www.news-medical.net

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