Periodic fasting or diets that mimic it can improve the effectiveness of endocrine therapy Breast cancer with positive hormone receptors, according to a study published in Nature.
The research carried out by teams from Italy and the Netherlands shows that this effect arises from the activation of the Glucocorticoid receptor (GR)which opens the possibility of using already approved corticosteroid medications to reproduce the benefits of fasting in the treatment of this type of cancer.
Hormone receptor-positive breast cancer accounts for approximately 75% of diagnoses of this disease. Although endocrine therapy is the mainstay of treatment in both the initial and advanced phases, primary or acquired resistance limits its effectiveness and promotes tumor progression, as described in detail Nature. This phenomenon has led to the search for strategies that improve the response to existing treatments.
The researchers observed that weekly 48-hour fasting cycles combined with tamoxifen achieved a synergistic antitumor effect in animal models. The multi-omics analyzes carried out on the tumors of mice subjected to this procedure revealed profound epigenetic reprogramming with large-scale activation of the Glucocorticoid and progesterone receptors (GR and PR)and a concomitant reduction in family activity AP-1 factorsknown for their role in tumor proliferation.
The study demonstrated that GR activation is essential for the enhancing effect of fasting on endocrine therapy. When the researchers eliminated GR in breast cancer cells, the combination of fasting and tamoxifen lost its ability to slow tumor growth.
Furthermore, exogenous administration of GR agonists such as dexamethasone reproduced the beneficial effects of fasting and promoted tumor regression in animal models.
In the clinical setting, the team studied breast cancer patients who were subjected to a fasting-like diet for five days as part of studies conducted in Italy. and it was recognized an increase in blood concentrations of cortisol and progesterone, hormones that activate GR and PR receptors.
Analyzes of tumor samples before and after dietary interventions revealed an inverse correlation between GR activation and markers of tumor proliferation, supporting the clinical relevance of the results observed in animals, the researcher reported Nature.
At the molecular level Fasting and diets that mimic it induce epigenetic reprogramming in tumor cells and activate genetic programs under the control of GR and PR, both known for their suppressive function in breast cancer. with positive hormone receptors.
The study identified inhibition of signaling pathways related to cell proliferation and reduction of mTOR activity, an important nutrient sensor in tumor growth. Furthermore, an increase in the expression of suppressor genes such as ZBTB16 was observed in association with GR activation.
One of the most relevant findings of the study is that the administration of Corticosteroidsas the Dexamethasone, may mimic the effects of fasting on the effectiveness of endocrine therapy.
In animal models, the combination of dexamethasone and tamoxifen managed to slow tumor growth and prolong survival without causing the side effects associated with prolonged fasting, such as weight loss.
In addition, dexamethasone reduced the expression of PD-L1 in certain immune cell populations, which may promote the immune system’s antitumor response.
The use of corticosteroids as an adjuvant to endocrine therapy represents a potential way to improve the treatment of hormone receptor-positive breast cancer, particularly in patients who cannot adhere to a restrictive diet.
However, Nature warns against it The results in humans are preliminary and the long-term safety of corticosteroids in this context requires careful evaluationbecause of her possible negative effects on the immune system, bones and metabolism. The study highlights the need for additional clinical trials to validate the effectiveness and safety of this strategy in clinical practice.
According to the authors, the administration of glucocorticoids could become a pharmacological alternative to fasting and make it possible to increase the effectiveness of endocrine therapy in hormone receptor-positive breast cancer through an approach already available in the clinic.
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