Bioinformatics reveals new combinations of drugs to fight breast cancer

Emobileclinic Researchers’Corner

In spite of the avalanche of drugs available to treat breast cancer, resistance has remained a major challenge. Based on the study of cell signalling networks, the cell signals that drugs alter when they reach their target molecule, an exhaustive in silico analysis of the pairing of 64 therapeutic agents used to treat breast cancer (half already in use and the other half in clinical testing phase) has permitted researchers at the Institute for Research in Biomedicine (IRB Barcelona) to detect 10 new and previously untested combinations that show potential for the treatment of breast cancer. This finding was published by the Journal of Cancer Research.

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Seven of the 10 combinations tested in breast tumour cells in vitro have revealed a high level of synergy (the joint effect is greater than the sum of the individual effects) and one of these combinations has been validated in mice. The results in mouse models indicate that the combination of raloxifene and cabozantinib, two drugs prescribed by oncologists, “dramatically” boost the anti-tumour effects of each of the two drugs. Patrick Aloy says, “we identify many more synergistic combinations in silico than combinatorial assays do until now with high-performance lab techniques, and we can provide experimental details. This implies that prior computational analyses give better results and are more reliable”. The researchers point out that in 70% of the combinations tested, the joint effects of the two drugs is “much much greater” than the effect of each alone, and therefore the same effect could be achieved with a smaller dose.

In cancer management, including breast cancer, one of the challenges faced by patients and oncologists is the onset of treatment resistance. Cancer cells become “insensitive” to the drugs that should kill them. According to Samira Jaeger, “our analyses have allowed us to predict the signalling pathways that are inactivated by the joint action of two drugs,” she explained further that “by combining drugs, we aim to attack the tumour cell simultaneously from various flanks, thus making it more difficult for the cell to resist treatment, as the pathways that allow it to survive and proliferate will be knocked out the same time,” she explains.

Source

Patrick Aloy et.al (2016): Quantification of pathway crosstalk reveals novel synergistic drug combinations for breast cancer, Cancer Research, doi: 10.1158/0008-5472.CAN-16-0097