New drugs to tackle cancer cell weak spots could end ‘scattergun’ chemotherapy

In In The News by Barbara Jacoby

By: Nicola Harley


Scientists have identified weak spots in cancer cells that could be targeted and attacked by new precision drugs.

The findings could lead to personalised medicine that “reads” a cancer patient’s DNA and only attacks defective cells – in contrast to the scattergun approach of conventional chemotherapy, which attacks all dividing cells, including healthy ones, according to new research published in the journal Nature Reviews Cancer.

A major computational analysis by scientists at the University of Sussex and The Institute of Cancer Research (ICR), London, found a number of potential targets for drugs that exploit the inherent weaknesses of cancer cells.

Scientists analysed the patterns of mutations found in the DNA sequences of tumours from more than 5,000 cancer patients.

The team, jointly led by Dr Frances Pearl and Dr Bissan Al-Lazikani, focused on the “DNA repair” systems that protect the genetic information of the cell and are mutated in almost all cancers.

Breaking these systems for DNA repair allows cancer cells to divide uncontrollably and generate even more mutations, helping them become resistant to chemotherapy and radiation treatments.

Dr Pearl, who heads the bioinformatics research group at the University of Sussex, said: “Knowing which DNA repair processes are defective in an individual tumour allows us to target new drugs that are only toxic to cells with a particular pattern of mutations – ie cancer cells.”

One class of drug called PARP inhibitors already target DNA repair systems, she said.

They are being used in clinical trials to treat women with breast or ovarian cancers that have mutations in BRCA genes, and one of the class, olaparib, has recently been licensed for women with ovarian cancer in Europe and the US, according to the study.

Dr Pearl said: “This analysis shows that there are many other cancers where new targeted drugs could selectively kill tumours with DNA repair defects.

“This potentially means thousands more cancer patients could be saved from the horrible side-effects of chemotherapy by receiving precision medicine, which doesn’t kill the body’s healthy cells.”

Dr Al-Lazikani, team leader in cancer therapeutics at the ICR, said: “Only a small fraction of the proteins involved in cancer are targeted by current drugs, and we urgently need drugs that hit new targets.

“DNA repair proteins hold particular promise as new drug targets, and there are already some drugs coming through that exploit cancer’s inherent weaknesses in DNA repair.

“Using ‘big data’ analysis, our study has identified untargeted DNA repair proteins that look especially promising as the targets for new anti-cancer drugs.

“Such drugs would not only prove useful in their own right, but also potentially in combination with radiotherapy or other drugs to overcome treatment resistance.

“We hope this study will help speed up the development of new personalised cancer treatments.”

Professor Tony Carr, director of the University of Sussex’s genome damage and stability centre, said: “The University of Sussex is playing a vital role in this war against cancer, not just through cutting edge scientific discovery but through the work of our drug discovery colleagues at Sussex and ICR who are creating new medicines that have a real impact in the treatment and diagnosis of major human diseases.

“The more we discover, the more intelligent our weapons against cancer become, and the closer we get to the day when cures for this major killer will be found.”