Researchers from Oxford University (UK) have identified mutations in the gene SETD2 that make cancer cells vulnerable to a drug that inhibits the protein WEE1. The findings were presented at the National Cancer Research Institute conference (held 1–4 November 2015, Liverpool, UK).
Mutations are associated with both cancer growth and treatment resistance. In spite of this, these mutations can also be the weak point in the tumor. The researchers studied cancer cells with mutations in SETD2 and demonstrated that the cells could be killed by the WEE1-inhibiting drug AZD1775.
Timothy Humphrey, an author of the study from Oxford, commented “Mutations in SETD2 are frequently found in kidney cancer and some childhood brain tumors, so we were excited when we discovered that a new drug we were studying specifically killed cancer cells with this mutation.”
The team combined two factors to kill cancer cells, a concept known ‘synthetic lethality’. This results in reduced toxicity and more effective treatment than standard approaches because it can directly target cancer cells.
Co-author of the study Andy Ryan, also of the University of Oxford, explained: “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. 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.”
The team also identified a biomarker to test for SETD2-mutated tumors, a key finding that could be utilized immediately in cancer diagnosis.
Tim Maughan, Clinical Director of the Cancer Research UK/Medical Research Council Oxford Institute for Radiation Oncology, commented: “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.”
There is still progress to be made before a treatment is available. However, it is hoped that the findings of this study can be utilized to identify similar weak points in other cancers and lead towards personalized cancer therapy.