Stanford researchers solve 'chemical brain' mystery

While chemotherapy can save lives, cancer treatment often leaves patients with side effects, including cognitive impairments in processing speed, memory, executive function and attention

Currently, there are no FDA-approved drugs to alleviate these deficiencies

The National Cancer Institute (NCI) predicts a cancer survival rate of 21%

CRCI is a major neurotoxic side effect of chemotherapy, affecting more than 50% of patients with widely used chemotherapy drugs, including taxanes such as paclitaxel and platinum-based drugs such as cisplatin

Cognitive deficits were reported in up to 75% of patients with non-neurological cancers who received chemotherapy, as assessed by neuropsychological testing

Salvemini, the William Beaumont Professor of Pharmacology and Physiology and Chair of the St.

"Because of the multifactorial origin of CRCI, our current understanding of the underlying mechanisms of CRCI and its impact on cognition is limited," Salvemini said

In her latest paper, Salvemini and her team present the first evidence that chemotherapy alters an important cellular pathway called sphingolipid metabolism in key regions of the brain associated with cognitive function

Their findings fill a gap in the understanding of the molecular mechanisms of CRCI and identify a new target for therapeutic intervention with functional S1PR1 antagonists

Salvemini said: "Our findings are very interesting because two functional S1PR1 antagonists are already FDA-approved for the treatment of multiple sclerosis

In previous research, Salvemini pioneered research into the treatment of neuropathic pain, potentially providing the first alternative to ineffective steroids and addictive opioids

"Our work is very translational," Salvemini said.

Sphingosine-1-phosphate receptor 1 activation in the central nervous system drives cisplatin-induced cognitive impairment