Scientists Find Cancer Weak Spots For New Targeted Drugs

Scientists Find Cancer Weak Spots For New Targeted Drugs
New drugs could attack cells that have defective DNA-repair
processes - a hallmark of a cancer cell. (Image source)
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. The study is published in the journal Nature Reviews Cancer.

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

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. 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. But the development of new targeted drugs like these relies on identifying good targets. It is only because of huge advances in technology that such a large-scale analysis is now possible.

By using cutting edge computing techniques, the team have been able to examine much larger data sets than ever before. 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.

Using 'big data' analysis, the study 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.

The researchers hope this study will help speed up the development of new personalised cancer treatments.

Based on material originally posted by University of Sussex.