The baking ingredient has been shown by other researchers to inhibit tumor invasion and metastasis in mouse models of breast cancer. The current study by the Second Affiliated Hospital, Zhejiang University School of Medicine in China shows that bicarbonate also had positive effects in a randomized controlled study in human hepatocellular carcinoma (HCC) patients.

The scientists also carried out a non-randomized trial that achieved a near-identical result. Survival data gathered from the study also suggests that bicarbonate could potentially work as a life-saving combined treatment.

“By adding bicarbonate to an existing treatment, we were able to kill tumors more effectively,” says Professor Xun Hu, Deputy Director of the Zhejiang University Cancer Institute, and senior author of the current study.

“As magnetic resonance imaging of the tumor following treatment revealed that the tumor size didn’t always change, we looked at the changes in tumor volume instead. We found that tumor residues in patients treated with bicarbonate was six-fold less than in the group without bicarbonate. This could be particularly valuable when treating large tumors that can be unresponsive to therapy.”

While tumors are often glucose-deprived, it has previously been shown that lactic acidosis, a common factor in their development, helps protect cancer cells from this otherwise hostile environment. In the current study, the team attempted to treat HCC by using the alkaline ingredient bicarbonate to create the opposite environment, and combining this with glucose deprivation.

The research included a non-randomized study, involving 57 patients with a large HCC tumor, and a randomized controlled study, involving 20 patients with the same condition.

The recommended treatment for HCC is transarterial chemoembolization (TACE), a procedure which limits the blood supply to a tumor, although this is not always effective in larger tumors. While TACE can effectively deprive HCC tumors of glucose and other nutrients by obstructing the arteries that supply them, it also traps lactic acidosis in the tumor, which can actually protect cancer cells from glucose deprivation and restrict anticancer activity.

“In principle, infusing a basic chemical, such as bicarbonate, into the tumor during the TACE procedure could neutralize the acid and resume cancer cells’ vulnerability to glucose deprivation, killing them quickly,” says Hu.

To test this, the patients were treated with TACE either with or without bicarbonate infusion into the tumor. In the non-randomized controlled and the randomized study, the mean amount of tumor residue left following TACE treatment with bicarbonate was over six-fold lower than that in TACE treatment without bicarbonate. 100% of patients treated with TACE and bicarbonate saw an objective response to treatment (ranging from larger than 50% necrosis to complete necrosis in the treated tumor), while only 44.4% (non-randomized) and 63.6% (randomized) saw the same result with TACE alone.

“Our research showed that infusing bicarbonate into these tumors can lead to a much cleaner death in cancer cells than without bicarbonate. The early sign of improved survival for patients was also promising, although not conclusive. Larger clinical trials will now need to be carried out to verify these initial findings,” says lead author Professor Ming Chao.

He adds that while the study looked at the feasibility of combining glucose deprivation with bicarbonate therapy in relation to HCC, their findings might not be limited to this type of cancer alone, and could be explored in treating other malignant tumors.

Reference

The paper ‘A nonrandomized cohort and a randomized study of local control of large hepatocarcinoma by targeting intratumoral lactic acidosis’ can be freely accessed online at http://dx.doi.org/10.7554/eLife.15691. Contents, including text, figures, and data, are free to reuse under a CC BY 4.0 license.