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An important review, resulting from collaboration between Italian and American researchers and recently published in Jama Oncology, delves into the efficacy of PARP inhibitors in the treatment of breast cancer. The study emphasizes not only the current use of these drugs for patients with breast cancer associated with germline BRCA1/2 mutations (gBRCA1/2), but also their promising future applications.
Olaparib, introduced in 2014, was the first PARP inhibitor approved and targeted at patients with advanced ovarian cancer. This marked the beginning of the adoption of PARP inhibitors, which now include three other drugs approved for various types of cancer. Recently, olaparib has also been applied in adjuvant therapy for patients with HER2-negative breast cancer at high risk of recurrence and with germline BRCA1/2 mutations.
Research indicates that the benefits of PARP inhibitors extend beyond the treatment of metastatic breast cancer with germline BRCA1/2 mutations, also reaching patients with somatic BRCA1/2 mutations and germline PALB2 alterations. These drugs have proven effective in both metastatic and adjuvant contexts. Despite the advantages, resistance to PARP inhibitors is a common phenomenon, with long-term responses being less frequent compared to other tumors, such as ovarian cancer. Various strategies are currently being examined to overcome this resistance, including the development of new PARP inhibitors and the adoption of innovative combination strategies.
In particular, selective PARP1 inhibitors, which reduce the hematological side effects associated with PARP2 blockade, represent a promising opportunity for combination with chemotherapy, antibody-drug conjugates, and other targeted therapies. However, many questions remain unanswered, and the authors of the review emphasize the need for future studies to identify predictive biomarkers of response, integrate these drugs into the treatment of breast cancer in its various stages, and develop new strategies to overcome resistance mechanisms.
In this scenario, the integration of translational efforts in clinical trials to characterize the omic profile of tumors and develop preclinical models for therapeutic investigations is crucial. Concurrently, the development of new drugs with better safety profiles could significantly advance the research of new therapeutic combinations.
An important review, resulting from collaboration between Italian and American researchers and recently published in Jama Oncology, delves into the efficacy of PARP inhibitors in the treatment of breast cancer. The study emphasizes not only the current use of these drugs for patients with breast cancer associated with germline BRCA1/2 mutations (gBRCA1/2), but also their promising future applications.
Olaparib, introduced in 2014, was the first PARP inhibitor approved and targeted at patients with advanced ovarian cancer. This marked the beginning of the adoption of PARP inhibitors, which now include three other drugs approved for various types of cancer. Recently, olaparib has also been applied in adjuvant therapy for patients with HER2-negative breast cancer at high risk of recurrence and with germline BRCA1/2 mutations.
Research indicates that the benefits of PARP inhibitors extend beyond the treatment of metastatic breast cancer with germline BRCA1/2 mutations, also reaching patients with somatic BRCA1/2 mutations and germline PALB2 alterations. These drugs have proven effective in both metastatic and adjuvant contexts. Despite the advantages, resistance to PARP inhibitors is a common phenomenon, with long-term responses being less frequent compared to other tumors, such as ovarian cancer. Various strategies are currently being examined to overcome this resistance, including the development of new PARP inhibitors and the adoption of innovative combination strategies.
In particular, selective PARP1 inhibitors, which reduce the hematological side effects associated with PARP2 blockade, represent a promising opportunity for combination with chemotherapy, antibody-drug conjugates, and other targeted therapies. However, many questions remain unanswered, and the authors of the review emphasize the need for future studies to identify predictive biomarkers of response, integrate these drugs into the treatment of breast cancer in its various stages, and develop new strategies to overcome resistance mechanisms.
In this scenario, the integration of translational efforts in clinical trials to characterize the omic profile of tumors and develop preclinical models for therapeutic investigations is crucial. Concurrently, the development of new drugs with better safety profiles could significantly advance the research of new therapeutic combinations.
