PHILADELPHIA, Pennsylvania- A new type of drug against cancer originally intended for women with scarce hereditary forms of breast cancer and ovarian cancer can also help a wider band of patients, according to a small clinical study. The drug halted tumor growth in a third of men with a usually fatal form of advanced prostate cancer. Almost all those who responded had linked mutations in their tumors, indicating that the drug was a common cellular processes, researchers reported this week at the annual meeting of the American Association for Cancer Research (AACR).
The drug blocks an enzyme called poly (adenosine diphosphate [ADP] Ribose) polymerase (PARP), which helps cells repair a type of DNA damage. Oncologists are especially test PARP inhibitors in patients with ovarian and breast cancer born with mutations in BRCA1 and BRCA2 , two genes linked to the cancer most infamous. These mutations raise the risk of a woman breast and ovarian cancer, and the risk of a man's prostate cancer because they inactivate proteins that repair DNA damage that can lead additional stimulus cancer mutations. But the defects in the two genes also allow tumor cells vulnerable to PARP inhibitors, because the drugs interfere with DNA repair further tumor cells machines. This combination makes tumor cells unable to correct DNA damage and die, an idea known as synthetic lethality.
In December, the first PARP inhibitor, olaparib the AstraZeneca has received approval in the US and Europe for patients with ovarian cancer who had inherited a BRCA1 or BRCA2 mutation.
But some cancer patients who lack such mutations also saw their tumors shrink in the tests. A team led by Johann de Bono of the Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, both in London, suspected that these patients had inherited errors in other DNA repair genes or had acquired mutations in BRCA or other genes in a tumor as formed or increased. There are three years, a sequencing project revealed that such defects in DNA repair genes are frequent in tumors of advanced prostate.
To test their hypothesis, group and collaborators of Bono, whose funding was independent of AstraZeneca, the drug gave 50 men with metastatic castration-resistant prostate, which means that their tumors have stopped responding to drugs that block hormones that stimulate the growth of prostate cancer. Of the 49 men who remained in the trial, 33%, or 16 patients responded to the drug, according to three measures decreased levels of tumor cells in the patient's blood, lower levels prostate specific antigen blood biomarkers scans or imaging found that their tumors shrank. When the researchers sequenced the DNA of the tumor patients, they found their hunch was correct: Fourteen of 16 respondents had mutations in one or more of a repair genes dozen DNA in their tumors, and only two nonresponders had these mutations, reported Joaquin Mateo, a clinical fellow in the laboratory of Bono, at the meeting of the AACR. (While three speakers had inherited BRCA2 mutations, four apparently had new mutations in this gene.) Most of these patients responded to the drug for at least 6 months (four for more than 1 year) while those without these mutations usually have worsened within 3 months.
Although genetic testing of tumors are already used to determine whether certain drugs will work for several types of cancer, this is the first time researchers have found such a test for prostate cancer, group Bono said. Olaparib could offer a new option for these men: The trial shows "it's a good swat to this disease," said researcher on prostate cancer William Nelson of Johns Hopkins University in Baltimore, Maryland, during a press AACR conference, adding that the prospect of genetic tests to identify cancer patients with prostate that could benefit from olaparib "looks very promising."
the results also suggest that women of ovarian and breast cancer who do not have a BRCA inherited mutation could still meet PARP inhibitors, if they have DNA repair mutations in tumors group Bono said. Ursula Matulonis of the Dana-Farber cancer Institute in Boston, who presented the results at AACR olaparib a combined test with another drug for patients with breast cancer and ovarian cancer, said at the press conference that his team plans to explore this possibility by DNA testing of biopsies of patients.
0 Komentar