In the US one of the main causes of death among men is severe prostate cancer. This type of aggressive cancer is typically associated with BRCA2 mutation which is also linked with other types of cancer including breast, pancreas and ovarian cancers. The study was led by researchers Elena Castro, Nuria Romero-Laorden and David Olmos, at the Prostate Cancer Clinical Research Unit at the Spanish National Cancer Research Centre (CNIO).
The study points out one of the preventive measures of developing cancers. It is that one should carry its complete diagnosis from familial cancer prevention programmes if one of its family members is a patient of prostate cancer and a carrier of BRCA2 or any other DNA repaired mutated gene.
The study is published in the Journal of Clinical Oncology. This new study also sheds light on the fact that people with prostate cancer due to BRCA2 mutations face worst and unstable conditions and symptoms. Furthermore, these people also develop a poor response to standard treatments. The researchers are currently working on the benefits gained after using ovarian and breast cancer treatments on prostate cancer patients.
The new findings also describe the first early outcomes of the study PROREPAIR-B, led by CNIO researchers and conducted at the Instituto de Investigacion Biomedica de Malaga (IBIMA) and the Instituto de Genetica Medica y Molecular (INGEMM). The study holds the participation of 38 Spanish hospitals.
In the study, more than 400 men were followed for consecutive five years from 2013 in order to study and observe their genetic characteristics. These prostate cancer patients showed resistance to castration and hormone blockade; the researchers were eager to know the influence of both the things on the progression of the disease as well as their impact on the outcome of opted treatments.
Castro the lead author of the article said: “This is the first prospective study—that is, not looking back in time but watching for outcomes from the moment patients are diagnosed with advanced cancer—that shows BRCA2 mutations themselves, regardless of other factors, are responsible for poor prognosis and can have an impact on treatment responses.”
He further explained, “It should be noted that we identified germline mutations, although in a number of patients there were no familial cancer cases that might have indicated the presence of such genetic alterations. These mutations should be identified in patients with metastatic prostate cancer, since detecting such alterations is important for the diagnosis and management of the disease and for the patients’ families, whose risk of developing breast, ovarian or pancreatic cancer is increased.”
PROREPAIR-B is the first early prospective study which focused on a large group of people who were diagnosed with prostate cancer and were resistant to castration or showed hereditary alterations.
David Olmos, the lead author of the CNIO Prostate Cancer Clinical Research Unit and director of the project said: “Our study shows that treatment and follow-up protocols used in patients with advanced prostate cancer may be inadequate for men with BRCA2 mutations. We are currently studying the characteristics that make these tumors more aggressive and trying to establish new strategies to improve patient prognosis.”
Early Detection of Aggressive Prostate Cancer with PROREPAIR-B
Prostate cancer attacks men now and then in Spain and Western countries; it holds the second position among most frequent cancers all around the world. Early diagnosis of the condition has now tremendously increased the survival rate in the recent few years; however in Europe still it remains to be the third leading cause of cancer deaths in men.
Early diagnosis of prostate cancers increases the chances of better survival. In most of the cases, advanced prostate cancer is treated with hormone therapies but there are many who develop resistance to castration. While there are also some people whose body does not show an effective response to standard treatments. Usually, the bodies that show hindrance in androgen deprivation therapy live up to only 3 years.
PROREPAIR-B aims to find out the real cause and genetic markers which are responsible for the poor recovery of the patient. Further research about the genetic characteristics of the tumors can pave a path for future successful treatments.
The study mainly talks about different genetics patterns causing a hindrance in DNA repair mechanisms. The tumor cells are quite different from the normal cells especially on the basis of genetic alterations; thus, these cells require a very specialized and high DNA repair mechanism. Castro believes that her team “knew DNA repair is extremely important in prostate cancer. What we did not know was the proportion of patients in the population with advanced stage disease and hereditary mutations.”
According to the study 3% of the patients are the carriers of the BRCA2 mutation, however, this percentage rises to 16% if the DNA repair genes are also considered. Castro says: “This proportion may seem comparatively low but it comprises a significant number of patients, given the high incidence of prostate cancer.”
A Birth to New Treatment
The researchers firmly believe that much more work is needed on existing therapies and new drugs should be further observed to improve the treatment strategies. There are some effective drugs which interfere with the regular mechanism of DNA repairing as those cells which fails to recover from the genetic defects die.
These drugs are called PARP inhibitors. These drugs are efficiently being used to treat ovarian cancers; however, they are under clinical trials for the treatment of prostate cancers. There is also another well-known drug Carboplatin which is also used to treat ovarian and breast cancers. The US Department of Defense has funded Spain to carry out clinical trials in order to analyze the effectiveness of Carboplatin for prostate cancer and DNA-repair defects.