Oxford researchers have found the 'Achilles heel' of certain cancer cells - mutations in a gene which could be targeted with a new drug to kill cancer cells that are resistant to treatment.
It is well known that mutations drive cancer cell growth and resistance to treatment. However, these mutations can also become a weak point for a tumour.
The researchers from University of Oxford in UK found that was the case for cancer cells with mutations in a key cancer gene called SETD2.
"Mutations in SETD2 are frequently found in kidney cancer and some childhood brain tumours, so we were excited when we discovered that a new drug we were studying specifically killed cancer cells with this mutation," said study author Timothy Humphrey from Oxford Institute for Radiation Oncology.
Researchers showed that cancer cells with a mutated SETD2 gene were killed by a drug called AZD1775 that inhibits a protein called WEE1.
The team achieved this by exploiting the concept of 'synthetic lethality', where a combination of two factors kills a cancer cell.
This has the potential to be a less toxic and more effective treatment than more standard approaches because it can specifically target cancer cells.
"When WEE1 was inhibited in cells with a SETD2 mutation, the levels of deoxynucleotides, the components that make DNA, dropped below the critical level needed for replication," said co-author Andy Ryan, from University of Oxford.
"Starved of these building blocks, the cells die. Importantly, normal cells in the body do not have SETD2 mutations, so these effects of WEE1 inhibition are potentially very selective to cancer cells," Ryan said.
The research team have also developed a biomarker test to identify SETD2 mutated tumours, something that can be used immediately in cancer diagnosis.
"This novel and exciting finding provides a new scientific basis for precision targeting of some cancers which are currently very difficult to treat, and we are now taking these findings into clinical trials," said Tim Maughan, Clinical Director of the Cancer Research UK/ Medical Research Council Oxford Institute for Radiation Oncology.
While there is still work to do before a treatment is available, the hope is that these findings will help to target other cancers with similar weak points and provide a step towards personalised cancer therapy, researchers said.
