In the following paragraphs, we will set out the major targeted drug that have received indications in breast cancer, both in the localized and in advanced disease, referring to the specific target (hormonal receptors, HER2, VEGF, m-TOR, PARP etc ...).
Recently, drugs directly targeting DNA repair mechanisms, such as PARP inhibitors, have emerged as attractive candidates for the future molecular targeted-therapy in breast cancer.
PARP inhibitors have been widely tested in clinical trials, especially for the treatment of breast cancer and ovarian cancer, and were shown to be highly successful.
Thus, whether the cancer tissue of origin is clearly associated with Lynch syndrome or not yet clearly established as a Lynch syndrome-related cancer (e.g., breast cancer), establishing the tumor to be dMMR/MSI-H is necessary to predict possible benefit and endorse the use of pembrolizumab.Ovarian cancers that develop in <i>BRCA</i> germline mutation carriers are so often related to the inherited mutated <i>BRCA</i> as the predisposing factor that testing the tumor for the footprint of <i>BRCA</i>-related ovarian cancer (<i>BRCA</i> loss of heterozygosity) is not necessary for use of the PARP inhibitor therapy olaparib.
Interestingly, CDK12 protein absence was associated with reduced expression of a number of DDR proteins including ATR, Ku70/Ku80, PARP1, DNA-PK, and γH2AX, suggesting a novel mechanism of CDK12-associated DDR dysregulation in breast cancer.
The PARP inhibitor olaparib is efficacious as monotherapy and has potential application in combination with endocrine therapy for the treatment of breast cancer.
The consistent observation that brain metastases of breast cancer tend to have higher HRD measures may raise the possibility that brain metastases may be more sensitive to PARP inhibitor treatment.
Poly-ADP ribose polymerase 1 (<i>PARP1</i>) is clinically important because of its synthetic lethality with breast cancer allele 1 and 2 mutations, which are causative for inherited breast and ovarian cancers.
<i>BRCA2</i> reversion mutations were detected in cfDNA prior to PARP inhibitor treatment in a patient with breast cancer who did not respond to treatment and were enriched in plasma samples after PARP inhibitor therapy.
PARP inhibitors have shown promising results in early studies for treatment of breast cancer susceptibility gene (BRCA)-deficient breast cancers; however, resistance ultimately develops.
PSP score-based classification of The Cancer Genome Atlas breast cancer suggested that a subset of patients with limited therapeutic options would be expected to benefit from PARP-targeted drugs.
Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially breast and ovarian cancers, and tumor cell lines deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition.
Poly (ADP-ribose) polymerase 1 (PARP1) is overexpressed in a variety of cancers, especially in breast and ovarian cancers; tumor cells that are deficient in breast cancer gene 1/2 (BRCA1/2) are highly sensitive to PARP1 inhibition.
Using immunohistochemistry on tissue microarrays, we evaluated subcellular NHERF1, BRCA1 and PARP1 expression in 308 BCs including a subgroup (n=80) of triple negative BCs (TNBCs).
<b>Purpose:</b> To explore whether a cross-talk exists between PARP inhibition and PD-L1/PD-1 immune checkpoint axis, and determine whether blockade of PD-L1/PD-1 potentiates PARP inhibitor (PARPi) in tumor suppression.<b>Experimental Design:</b> Breast cancer cell lines, xenograft tumors, and syngeneic tumors treated with PARPi were assessed for PD-L1 expression by immunoblotting, IHC, and FACS analyses.