Scientists uncover a powerful biological mechanism where fasting enhances standard therapy and slows resistance – with clues for new treatment strategies
A groundbreaking study published in Nature has uncovered how periodic fasting dramatically improves the effectiveness of endocrine therapy in hormone‑receptor positive (HR+) breast cancer, the most common subtype affecting millions of women worldwide.
Why This Matters
HR+ breast cancer – driven by estrogen receptors – relies heavily on endocrine therapies like tamoxifen to block tumour growth. But over time, many patients develop resistance and tumours begin to grow again despite treatment.
The new research shows that fasting triggers deep biological changes in cancer cells that make them much more responsive to therapy, revealing a mechanism that could help doctors boost treatment success.
What Fasting Does Inside Tumours
In animal models, researchers found that periodic fasting combined with tamoxifen didn’t just slow tumour growth , it enhanced tumour regression far beyond what the drug alone could do.
Here’s how fasting works at the molecular level:
Epigenetic Reprogramming
Fasting alters the tumour’s epigenetic landscape , the way genes are turned on and off especially when combined with standard therapy.
This leads to:
Activation of glucocorticoid receptor (GR) and progesterone receptor (PR) signaling , both of which help suppress tumour growth.
Reduced activity of AP‑1 transcription factors, which normally fuel cancer progression.
Glucocorticoid Receptors: A Key Player
The team showed that fasting specifically boosts GR signaling inside the tumour. When GR was genetically removed in experiments, the fasting benefit disappeared – proving that GR activation is essential for this effect.
Even more exciting, simply giving medicines that activate GR mimicked the effects of fasting, suggesting a new drug strategy for patients who find fasting difficult.
Evidence That This Happens in Patients Too
The researchers didn’t stop at mice – they also looked at human patients on fasting‑mimicking diets (a low‑calorie, low‑protein, low‑sugar diet designed to replicate the effects of fasting).
These patients showed:
Increased blood levels of cortisol and progesterone – hormones that activate GR and PR in tumour cells.
Tumours with stronger GR activation had lower levels of proliferation markers, indicating reduced tumour growth activity.
What This Could Mean for Breast Cancer Treatment
This research suggests two major possibilities:
- Dietary approaches (like fasting or fasting‑mimicking diets) might be used safely along with current therapies to enhance treatment outcomes.
- GR‑targeting drugs could be developed to replicate fasting’s anti‑tumour effects without the need for strict diets.
Such strategies could help delay or prevent therapy resistance – one of the biggest challenges in breast cancer care.
A New Path Forward
While fasting isn’t suitable for everyone, and clinical guidelines will require careful study, this discovery gives researchers a mechanistic roadmap for boosting the effectiveness of life‑saving therapies.
According to the authors, glucocorticoid activation is a pivotal switch that explains why fasting helps tamoxifen work better and importantly, it opens the door to new drug combinations that could transform how HR+ breast cancer is treated.
Reference: Fasting boosts breast cancer therapy efficacy via glucocorticoid activation
