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Triple-Negative Breast Cancer (TNBC) is a very aggressive subtype of breast cancer that is distinguished by the lack of Human Epidermal Growth Factor Receptor 2 (HER2), Progesterone Receptors (PR) and Estrogen Receptors (ER). TNBC's lack of receptors renders it resistant to HER2-targeted therapies and hormone therapy, which poses a major management problem. Effective targeted therapy for TNBC is therefore desperately needed. In this paper, new approaches to targeted therapy for TNBC are reviewed with an emphasis on their mechanisms, clinical utility and future directions.

TNBC makes up 10%-20% of all breast cancer cases and is more common in African American and younger women. With a range of genetic and epigenetic changes, it is typified by considerable molecular heterogeneity. These comprise changes to pathways like PI3K/AKT/ mTOR and MAPK, as well as mutations in genes like TP53 and BRCA1/2. When compared to other breast cancer subtypes, TNBC has a worse prognosis and a greater recurrence rate due to its high molecular variety and lack of specific receptors, which make treatment more difficult. Inhibitors of Poly (Adp-Ribose) Polymerase (PARP) have demonstrated potential in the treatment of Triple Negative Breast Cancer (TNBC), especially in individuals with BRCA1/2 mutations. An enzyme called PARP is essential in DNA repair; when it is inhibited, DNA damage builds up and eventually results in cancer cell death. A major development in the treatment of BRCA-mutated breast cancer has been the approval of PARP inhibitors such as olaparib and talazoparib. Improved Progression-Free Survival (PFS) in patients with TNBC who carry a BRCA mutation has been the result of clinical trials demonstrating their effectiveness.

TNBC patients may benefit from immunotherapy, especially with immune checkpoint inhibitors. Checkpoint inhibitors specifically target proteins that cancer cells employ to avoid the immune system, such as CTLA-4 and PD-1/PD-L1. PD-1/PD-L1 inhibitors pembrolizumab and atezolizumab have demonstrated promising outcomes in clinical trials. For instance, the IMpassion130 study showed that for patients with PD-L1-positive TNBC, atezolizumab plus nab-paclitaxel increased PFS and OS. Androgen Receptors (AR) are expressed in 10%-20% of TNBC cases, which presents a possible therapeutic target. In ARpositive TNBC, AR antagonists including enzalutamide and bicalutamide have been studied. Clinical trials in the early stages have demonstrated that AR antagonists can have a positive impact on patients' health, with some even managing to stabilize their disease. To better understand the function of AR antagonists in TNBC and discover response biomarkers, more research is required.

ADCs, which combine the cytotoxicity of chemotherapeutic drugs with the specificity of antibodies, represent a revolutionary approach to targeted therapy. The ADC sacituzumab govitecan, which targets Trop-2, has demonstrated notable effectiveness in TNBC. Sacituzumab govitecan was found to improve PFS and OS in patients with metastatic TNBC as compared to chemotherapy in the ASCENT study. Because of this, it has been approved to treat metastatic TNBC, providing a fresh therapy choice for this difficult illness. Therapeutic targets for TNBC often target the PI3K/AKT/mTOR pathway. Clinical trials are being conducted on inhibitors of this pathway, including PI3K inhibitor alpelisib and mTOR inhibitor everolimus. According to preliminary findings, focusing on this pathway may have therapeutic benefits, particularly when paired with other treatments. But more investigation is required due to the pathway's intricacy and the possibility of resistance mechanisms.

There are still a number of obstacles to overcome in the therapy of TNBC, even if these new treatments give patients hope. The emergence of resistance to targeted medicines is a significant obstacle. Through a variety of processes, including activating different pathways or accumulating mutations that make the therapy ineffective, cancer cells can adapt. Comprehending these resistance pathways is essential to creating combination treatments that either avoid or overcome resistance. Finding trustworthy biomarkers to forecast response to focused treatments is another difficulty. Because TNBC is heterogeneous, not every patient will benefit from a particular treatment. By assisting in the customization of therapy for each patient, biomarkers can enhance results and reduce needless toxicity. The goal of ongoing research is to identify and validate these biomarkers. Improved preclinical models that appropriately capture the intricacy of TNBC are also necessary. Often, the heterogeneity and tumor microenvironment of TNBC are not adequately reflected in traditional cell line models. More precise platforms for evaluating novel treatments and comprehending their mechanisms of action are being created, including organoid models and Patient-Derived Xenografts (PDXs).

Finally, Targeted therapy for triple-negative breast cancer is a fast changing field with various techniques showing promise. Among the most promising areas of study are inhibitors of the PI3K/AKT/mTOR pathway, immune checkpoint inhibitors, AR antagonists, ADCs and PARP inhibitors. The emergence of resistance, the search for predictive biomarkers and the requirement for improved preclinical models are some of the major obstacles that still need to be overcome. For patients with this aggressive form of breast cancer, further research and clinical trials are necessary to overcome these obstacles and improve their prognosis. There is hope that as our knowledge of TNBC biology expands, more tailored and efficient treatments will be made available, giving individuals fighting this aggressive illness newfound hope.