Dr. Manasi Das did her Master in Life Sciences from Sambalpur University, Odisha, India. After that, she did her Ph.D. from the Institute of Life Sciences, Bhubaneswar, Odisha, India, under the supervision of Dr. Sanjeeb Kumar Sahoo, where she studied on Nanodrug delivery for breast cancer therapy. Presently, she is Postdoctoral Fellow in the Department of Medicine, University of California, San Diego, USA. Her research focuses on understanding the role of time-restricted feeding/eating intervention in breast cancer.
Dr. Deepak Kumar did his Master in Biotechnology from PG Dept. of Biotechnology (Supported by Dept. of Biotechnology, Govt. of India) Utkal University, Odisha, India. After that, he did his Ph.D. from the Institute of Life Sciences, Bhubaneswar, Odisha, India, under the supervision of Dr. Nrisingha Dey, where he studied on Development of promoters with enhanced transgene expression. Presently, he is a Project Scientist in the Department of Medicine, University of California, San Diego, USA. His research focuses on (1) understanding the mechanism of RNA splicing factor involved in obesity, liver metabolism and liver cancer initiation, and progression, (2) investigating the therapeutic potential of time-restricted feeding for obesity induced metabolic disease. Here, Manasi and Deepak talks about their work titled “Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models” published in Nature communications.
How would you explain your papers key results to the non-scientific community?
We found that restricting access to food to an eight-hour window when physical activity is highest delayed breast cancer formation, inhibited growth of existing tumors, and reduced cancer metastases to the lung. We observed this inhibition in multiple models of postmenopausal breast cancer in obese mice with both hormone-dependent tumors and triple-negative, hormone-independent tumors.
What are the possible consequences of these findings for your research area?
We had previously published that when mice overeat a highly caloric diet and become obese, breast cancer is greatly accelerated. We had also found that feeding the mice a similar diet but supplementing with omega-3 fatty acids would reduce insulin resistance and tumor growth. Our group, and others, had published that using time-restricted access to food (TRF) could similarly reduce insulin resistance, and we now report in our recent publication that TRF inhibits breast cancer. Is this mouse study relevant to human health? Although large scale studies have not been performed, a number of small studies have shown that increasing the length of time between the last meal of the day and breakfast the next morning (i.e. increasing the length of the overnight fast), which is analogous to TRF in mice, has beneficial effects in humans by improving metabolism and reducing insulin resistance. One of our colleagues Dr. Sears has published pidemiological evidence that a longer overnight fast is associated with reduced risk of breast cancer, and similar associations have been seen in prostate and pancreatic cancer. We believe our findings in the mouse study provide strong, mechanism-based evidence for adopting time-restricted eating to reduce insulin resistance and protect against obesity-driven breast cancer in humans. Our findings support the possibility that a simple dietary manipulation through time restricted eating might be a potential non-pharmacological and practical way to achieve beneficial effect in breast cancer therapy.
What was the exciting moment (eureka moment) during your research?
The most exciting moment was during the first TRF experiments with hormone-dependent breast cancer. This model involved introducing breast cancer tumor cells into the mammary glands in mice. The cells were already cancerous and we were just measuring how quickly the tumor grew. We were delighted to see that the tumors in the obese mice on TRF grew much slower, at a rate no different from that in lean, healthy mice. So the TRF had completely eliminated the effect of obesity to accelerate tumor growth.
What do you hope to do next?
The beauty of prolonged overnight fasting is that people are asleep during most of the fasting period, so they are not bothered by hunger. This is very different from other forms of intermittent fasting that involve reducing caloric intake during the day. If prolonged nightly fasting is proven to be effective at preventing cancer incidence or reoccurrence, it would be relatively easy to draft nutritional recommendations for cancer patients. We are currently pursuing a randomized control clinical trial in cancer survivors to see if prolonged nightly fasting will prevent a recurrence.
Where do you seek scientific inspiration?
Obesity is a worldwide health problem. Obese populations have a higher incidence of endometrial, colorectal, prostate, pancreatic and postmenopausal breast cancer. One in eight women will be diagnosed with breast cancer during their lifetime. Breast cancer is strongly associated with age as the incidence is 42/100,000 for women <50 years of age, but 327/100,000 for age >50 and 398/100,000 for age >60. The epidemiologic evidence for obesity – breast cancer connection is particularly strong: several studies across diverse populations show that breast cancer risk increases by 40% in obese post-menopausal women. Obesity is associated with a greater than 2-fold increase in breast cancer risk in post-menopausal women. Furthermore, obesity is associated with a higher incidence of aggressive triple-negative tumors and reduced survival, regardless of menopausal status.
How do you intend to help Indian science improve?
Considering the increased risk obesity poses for several cancer types, practical strategies to reduce obesity’s harmful sequelae could have a far-reaching impact. Dietary intervention is a potential means to mitigate this risk. Dieting (caloric restriction) and intermittent fasting are beneficial to metabolic health and reverse many of the detrimental effects of obesity. These beneficial effects also extend to cancer. For many years, it has been known that caloric restriction inhibits tumor growth in animals and sensitizes cancer cells to chemo- and radiation therapy. Despite promising animal data and considerable evidence for human health benefits, clinics have not adopted these dietary interventions as most of these fasting regimes require active intervention by nutritionists or clinical researchers to ensure compliance. While these interventions may work in the short-term to correct metabolic dysfunction, they are not suitable for long-term use at home due to low compliance in the obese population, particularly as daytime fasting is associated with hunger and irritability. A prolonged nightly fasting nutritional intervention, which has the same health benefits as a caloric restriction but is easier to maintain, would greatly increase long-term compliance and have a major impact on Indian health.
Das, M., Ellies, L.G., Kumar, D. et al. Time-restricted feeding normalizes hyperinsulinemia to inhibit breast cancer in obese postmenopausal mouse models. Nat Commun 12, 565 (2021). https://doi.org/10.1038/s41467-020-20743-7
Press release: https://health.ucsd.edu/news/releases/Pages/2021-when-not-what-obese-mice-ate-reduced-breast-cancer-risk.aspx and https://www.nutritioninsight.com/news/time-restricted-feeding-may-inhibit-breast-cancer-shows-study-of-obese-postmenopausal-mice.html