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Clinical and genomic characterization of a deadly type of prostate cancer

24 July 2018 14:05

The new study, which was attended by 202 men with metastatic and resistant to cancer treatment predstetlnoy cancer, showed that a surprisingly large number of cancers - about 17% - belong to the most lethal subtype of metastatic prostate cancer.

It used to be that these cancers account for less than 1% of all prostate cancers.

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The study was conducted by University of California in San Francisco and published in the online edition of the «Journal of Clinical Oncology». Scientists have found that this subtype is a cancer of the prostate (t-SCNC) - small cell neuroendocrine prostate cancer requiring immediate therapy - can be effectively treated with targeted drugs which are being developed or tested in clinical trials.

"Imagine that aggressive treatment of hormone-resistant prostate cancer - a cake - said the scientist. - We want to share the cake, depending on the tumor characteristics and to develop treatment protocols that are adapted to the individual pieces of the pie, and based on the distinctive genetic cancer mutations and gene expression. "

The research team identified specific genetic mutations and gene expression patterns that are detected in the t-SCNC, but differ from the most common type of prostate cancer, known as adenocarcinoma. observed increased activity of specific proteins transkritsionnyh factors among samples identified in t-SCNC - proteins that "comprise" production of other proteins that promote the growth of cancer.

Two transcription factors, characterized by excessive activity of a t-SCNC, are targets for drugs that are being tested in clinical trials. Scientists have also discovered mutations that have never been observed in t-SCNC, but which play an important role in the development of many adenocarcinomas.

Treatment aimed at specific mutation of prostate cancer are not available in standard practice. Traditional treatment is hormone therapy and chemotherapy. However, as the number of targeted types of treatment increases, genetic analysis of tumors is becoming increasingly valuable to the patient.

According to the American Cancer Society, in 2018 29,430 people will die from prostate cancer. This is the second most common cause of cancer death, after lung cancer. At the time of initial diagnosis in one patient out of ten found a tumor that has spread beyond the prostate gland, and it is difficult to cure.

In developed cancer stages additional mutations and gene expression changes in the model leads to the appearance of cells resistant to treatment. These resistant cells clones and started during cell division, leading to the growth and spread of tumors. Patterns of gene mutation observed in the study show that the t-SCNC arises from preexisting adenocarcinoma.

"In metastatic prostate cancer hormone therapy is necessary to patients, since hormonal treatments prolong survival. But these drugs can not cure the disease. Almost every cancer patient becomes resistant. The only question is when it will happen. We want to find out why cancer becomes resistant, and we believe that the appearance of t-SCNC is an important mechanism by which cancer cells evade treatment "- the researchers reported.

Scientists have documented that cancer cells from study participants have become resistant to traditional hormonal treatment known as androgen suppression therapy.
Among patients who stopped before all respond to hormonal treatment of the second line (or abarateron enzalutamid), the survival rate of participants with a subtype of t-SCNC averaged 36.6 months compared with 44.5 months in the other volunteers.

In 160 participants it was sufficient biopsy specimens to classify cancer. Scientists have discovered t-SCNC in 27 men out of 160. They studied genetic mutations and gene activation in tumor cells and genetic mutation patterns identified, which have been associated with t-SCNC and poorer survival.



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