Early-stage research led by the Institute of Cancer Research (ICR) and Sun Yat-sen University in China has demonstrated that a drug currently used to treat epilepsy could keep chemotherapy working for longer in stomach cancer patients.
The team found that cancer’s resistance to chemotherapy could be reversed by targeting lactate, which builds up as cancer cells convert nutrients to energy in a process called glycolysis.
Clinical trials have now been launched to evaluate whether the lactate production-targeting epilepsy drug, Biocodex’s Diacomit (stiripentol), causes chemotherapy to work again in stomach cancer patients who have become resistant to treatment.
A pre-clinical study has already shown that the drug re-sensitised stomach cancers to chemotherapy, resulting in tumour shrinkage and prolonged survival.
The researchers first looked at tissue from 24 stomach cancer patients and found that lactate was most abundant in those that were chemotherapy-resistant.
During glycolysis, glucose is first turned into pyruvate and then lactate by an enzyme called LDHA, which stiripentol targets.
They then tested stiripentol and chemotherapy in mice with the disease and found that the combination reduced the size of tumours, with responses continuing to last for four weeks after treatment. In comparison, the tumours of mice treated with chemotherapy alone shrank for one week before starting to grow again.
The mice treated with stiripentol and chemotherapy survived for more than 70 days, while none survived for longer than 40 days after receiving chemotherapy alone.
Axel Behrens, professor of stem cell biology at the ICR, said: “In our early-stage study, we’ve seen that you can prevent the build-up of lactate and make a tumour that was resistant to chemotherapy become sensitive again – the treatment continues to work.
“The next step is to test this in a clinical trial, and it would be wonderful if we see the same results in people and give people with cancer precious extra time living well. As we already have a drug to target lactate in clinical use, this discovery could reach patients even sooner.”
The researchers also believe that lactate may be responsible for chemotherapy resistance in other cancers, as levels of LDHA are increased in pancreatic, lung and ovarian cancers.