Researchers identify a new pathway to treat ovarian cancer through its metabolism

Section of tumour tissue with BRCA2 mutations.
Section of tumour tissue with BRCA2 mutations.
Research
(15/05/2020)

Ovarian cancer has a high mortality: in fact, only 50% of patients survive after dive years of diagnosis, and it causes the annual death of about 300 women in Catalonia. Great part of these cancers show mutations in the genes BRCA1 and BRCA2, and can be treated with PARP protein inhibitors. However, many cases progress and develop resistance. A new article published in the journal EMBO Molecular Medicine describes a new therapeutic strategy based on metabolic drugs such as Metformin, which could be a new opportunity for the patients.

Section of tumour tissue with BRCA2 mutations.
Section of tumour tissue with BRCA2 mutations.
Research
15/05/2020

Ovarian cancer has a high mortality: in fact, only 50% of patients survive after dive years of diagnosis, and it causes the annual death of about 300 women in Catalonia. Great part of these cancers show mutations in the genes BRCA1 and BRCA2, and can be treated with PARP protein inhibitors. However, many cases progress and develop resistance. A new article published in the journal EMBO Molecular Medicine describes a new therapeutic strategy based on metabolic drugs such as Metformin, which could be a new opportunity for the patients.

This study, carried out by researchers from the ProCURE program, from the Catalan Institute of Oncology (ICO), from the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Barcelona (UB), shows that tumours with mutatuons in the BRCA genes are highly dependent on the oxidative metabolism and the inhibition of enzymes in this pathway, with drugs such as Metformin, stop the growth of tumours and cancer cells die. To reach these conclusions, researchers implanted human tumours in mice models and analysed patient samples.

The article describes how tumours use the oxidative metabolism to make the necessary DNA repair mechanisms work and keep the tumour alive. Cancer cells need a constant supply of energy to grow and can adopt its metabolism in different ways depending on the conditions under which they are. “This discovery sheds light to treat tumours with mutations in the genes BRCA1 and BRCA2 attacking its metabolism”, notes Professor Francesc Viñals, from the Department of Physiological Sciences of the UB and head of the project.

Researchers present Metformin as a potential treatment. This drug is a powerful inhibitor of the oxidative metabolic pathway that proved in animal and cell models to be able to stop the tumour growth inhibiting the DNA repairment. Also, it is approved for the treatment of diabetes and shows tolerance in humans, so its authorization for the use of these cancers would be fast and would need less investment.
 

Further information

Article reference: Á. Lahiguera et al. "Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors". EMBO Molecular Medicine, May, 2020. Doi: //doi.org/10.15252/emmm.20191121