A targeted drug that has shown promise in treating breast, ovarian and prostate cancer patients with few side-effects may also work for the most common type of womb cancer, according to a study in Science Translational Medicine.
A team from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) in London have shown that the new type of drug, called PARP inhibitors, can kill womb cancer cells that have a defective PTEN gene.
“Up to 80 per cent of the most common type of womb cancers have a defect in this gene, so there is potential for this drug to treat a significant number of women,” says study author Jorge Reis-Filho from the Breakthrough Breast Cancer Research Centre at the ICR.
“If these results are confirmed in a clinical trial, we would have an alternative treatment for advanced womb cancer that has far fewer side-effects than current treatments.”
The number of women suffering womb cancer in the UK is at its highest rate for 30 years, with more than 7,500 diagnosed a year and 1,700 deaths. It is the fourth most common cancer among women in both the UK and the US.
The most important treatment for womb cancer is surgery (a hysterectomy) but women may also be given radiotherapy, chemotherapy or hormone treatment depending on the type and stage of the cancer. All of these treatments carry significant side-effects. PARP inhibitors, by comparison, are a type of personalised medicine that exploits existing weaknesses in cancer cells. They kill cancer cells while leaving healthy cells relatively unaffected, which means fewer side-effects for patients.
PARP inhibitors – including the drug olaparib, which ICR scientists helped develop – are already being tested in patients who have cancer linked to BRCA mutations, including some breast and ovarian cancers.
Last year scientists from the Breakthrough Breast Cancer Research Centre at the ICR showed that, as well as BRCA1/2-mutant cancers, PARP inhibitors can also kill cancer cells with a faulty PTEN gene. Faults in the PTEN gene are common in a range of cancers – including breast, prostate, skin, womb and bowel cancers – so the finding raised the possibility that the drug may be used in a greater range of cancers.
In this latest study, a team from the Breakthrough Breast Cancer Research Centre at the ICR looked to confirm this finding specifically in womb cancers.
The scientists studied endometrioid endometrial cancer, a subtype which comprises about 75 to 80 per cent of all womb (endometrial) cancers. They scanned eight different types of endometrioid endometrial cancer cells to determine whether they had a fault in the PTEN gene or not. They then tested the cells to find out whether PARP inhibitors would kill them, and compared it with the genetic screening results. They found the cells with the genetic fault were unable to repair the DNA damage caused by PARP inhibitors themselves, while cells with a normally functioning PTEN gene were unharmed.
To confirm the results, the team altered mutated cells to restore the PTEN gene function and found they gained relative resistance to the drug.
The team concluded that as womb cancer cells with malfunctioning PTEN genes were highly sensitive to PARP inhibitors in a laboratory setting, the next step will be to test PARP inhibitors in patients with PTEN-deficient womb cancer.
ICR
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