Study in mice shows fixing body rhythm in cancer may shrink tumours

New Delhi, Dec 16 (PTI) A study in mice has shown that cancer could disrupt the body's corticosterone-circulating rhythm, and fixing it led to a significant shrinking of tumours -- findings that may help boost the effectiveness of existing treatments.

Studies have shown evidence that supports targeting the body's circadian clock for mitigating and treating cancer by improving rhythms and time of medication, also known as 'chronotherapy'.

Author Jeremy Borniger, assistant professor at Cold Spring Harbor Laboratory, a US-based private, non-profit laboratory, said the research team did not treat the mice with anti-cancer drugs.

"We're focused on making sure the patient is physiologically as healthy as possible. That itself fights the cancer. This might one day help boost the effectiveness of existing treatment strategies and significantly reduce the toxicity of many of these therapies," Borniger said.

The human body is known to depend on a feedback loop involving the hypothalamus (H), pituitary gland (P), and adrenal glands (A) -- the HPA axis -- to ensure regular day-night or 'diurnal' rhythms.

In mice induced with breast cancer, the researchers found that the tumours can disrupt the day-night rhythms of corticosterone -- the stress hormone, levels of which typically rise and fall naturally through the day.

"Even before the tumours were palpable, we see about a 40 or 50 per cent blunting of this corticosterone rhythm. We could see that happening within three days of inducing the cancer, which was very interesting," Borniger said.

Looking at the hypothalamus in the mice's brains, the researchers found key neurons were locked into a hyperactive, yet low-output state.

Stimulating the neurons to mimic the normal day-night cycle restarted regular rhythms of the stress hormone, which pushed anti-cancer immune cells into breast tumours and shrank them significantly.

"Enforcing this rhythm at the right time of day increased the immune system's ability to kill the cancer -- which is very strange, and we're still trying to figure out exactly how that works," Borniger said.

"The interesting thing is that if we do the same stimulation at the wrong time of day, it no longer has this effect. So, you really need to have this rhythm at the right time to have this anti-cancer effect," the author said.

The authors "demonstrate that breast tumour-bearing mice exhibit blunted GC (glucocorticoids) rhythms and a loss of diurnal rhythms in the activity of paraventricular hypothalamic neurons expressing corticotropin-releasing hormone." "Using chemogenetics to stimulate neurons (expressing corticotropin-releasing hormone) at different times of day, we show that stimulation just before the light-to-dark transition restores normal GC (glucocorticoids) rhythms, reduces tumour progression, and increases intra-tumour effector T cells," they said.

The researchers are now looking to the processes through which tumours disrupt the body's healthy rhythms. PTI KRS KRS RT RT