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Prostate: there is a targeted therapy that saves men

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Prostate: there is a targeted therapy that saves men

Metastatic prostate cancer resistant to testosterone-suppressing drugs, associated with the development of the tumor, is the most difficult to treat form of all prostate cancers. Today, however, thanks to the development of molecular target therapies, the scenario is starting to change for the better. The target is a mutation known as BRCA, the Angiolin mutation, involved in breast and ovarian cancer.

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Hitting it by using standard therapy based on enzalutamide as the first treatment in combination with the so-called PARP inhibitor talazoparib – capable of canceling the DNA replication mechanisms of diseased cells – significantly increases disease-free survival while preserving the quality of life of the sick. A result reaffirmed in Chicago during the congress of the American Society of Clinical Oncology (ASCO), the main world event dedicated to the fight against cancer.

Prostate cancer

According to the latest edition of “The numbers of cancer 2022” created by the Italian Association of Medical Oncology (AIOM) every year, in our country, there are over 40 thousand new diagnoses of prostate cancer. This form of cancer is the most frequent neoplasm in men over 50 years of age and occupies third place in the scale of cancer mortality, especially in men over 70 years of age. While the chances of a cure are high for cases diagnosed at an early stage and for those that develop slowly, the real challenge is metastatic prostate cancer.

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When the tumor becomes resistant

Depending on the stage of evolution we proceed with different therapeutic strategies which include surgery, chemotherapy and hormone therapy. When the disease is in metastasis, the first-line treatment involves the so-called androgen deprivation, a strategy in which drugs capable of inhibiting the production of testosterone, the hormone that stimulates the growth of tumor cells, are administered. Although it is an effective strategy, it is not uncommon for the person to no longer respond to treatment. This is the case of metastatic castration-resistant prostate cancer, the most difficult form of prostate cancer to cure.

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The role of PARP inhibitors

In recent years, thanks to the molecular analysis of the disease, some castration-resistant forms have begun to be tackled with greater success thanks to the administration of PARP inhibitors, molecules that interfere with the mechanisms that the cell puts in place to repair DNA damage . This is the case of tumors with “homologous recombination defect”. The possibility of interfering with this mechanism makes the tumor “rich” in alterations to the point of undergoing cell death due to too much damage.

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I study TALAPRO-2

Thanks to the accumulation of evidence of the utility of PARP-inhibitors in those tumors that have a homologous recombination defect, a further clinical trial was recently carried out to evaluate the first-line association of standard therapy with enzalutamide with the PARP-inhibitor talazoparib whether or not the homologous recombination defect is present. TALAPRO-2, this is the name of the study, had as its objective the evaluation of disease-free progression (PFS), or the period of time in which the disease, although present, does not progress. This is an important parameter since the increase in PFS is an index of efficacy of the treatments and is generally related not only to a prolongation of the patient’s survival but also to a better quality of life.

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The first results, presented in March at the ASCO Genitourinary Symposium, showed that the combination of the two drugs led to a 37% reduction in the risk of disease progression or death compared with enzalutamide alone. Italy made a great contribution to the experimentation, with 7 hospital centers involved in recruiting the patients who participated in the study. Now at the ASCO congress in Chicago, in addition to confirming the data obtained, the results of an analysis on the quality of life of patients in relation to the treatment were presented. The analyzes showed that the better disease control obtained with the combination translated into a maintenance of quality of life. Important results that will now have to be evaluated in the long term. The hope is that lengthening PFS will also translate into improved overall survival from the disease.

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