Recent advances in targeted strategies for triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC), a highly aggressive subtype of breast cancer, negatively expresses estrogen receptor, progesterone receptor, and the human epidermal growth factor receptor 2 (HER2). Although chemotherapy is the main form of treatment for patients with TNBC, the effectiveness of chemotherapy for TNBC is still limited. The search for more effective therapies is urgent. Multiple targeted therapeutic strategies have emerged according to the specific molecules and signaling pathways expressed in TNBC. These include PI3K/AKT/mTOR inhibitors, epidermal growth factor receptor inhibitors, Notch inhibitors, poly ADP-ribose polymerase inhibitors, and antibody–drug conjugates. Moreover, immune checkpoint inhibitors, for example, pembrolizumab, atezolizumab, and durvalumab, are widely explored in the clinic. We summarize recent advances in targeted therapy and immunotherapy in TNBC, with the aim of serving as a reference for the development of individualized treatment of patients with TNBC in the future.

Progression from ductal carcinoma in situ to invasive breast cancer: molecular features and clinical significance

“…Targeted drugs that intended for BRCA1/2 mutations, intracellular signaling pathways, immune checkpoint have brought great opportunities to improve the prognosis of TNBC patients. 374 …”

“…Ongoing research is exploring additional targeted therapies to inhibit intracellular signaling pathways such as PI3K/AKT/mTOR, EGFR, Notch signaling, and STAT3 signaling, aiming to evaluate their safety and effectiveness in TNBC patients. 374 However, the current therapeutic options for TNBC are limited compared to ER-positive and HER2-positive breast cancer due to the absence of well-defined targets and the inherent heterogeneity of TNBC itself. As a result, effectively treating TNBC remains a significant challenge that needs to be addressed.…”

“…For example, anti-angiogenic drugs like VEGF/VEGFR inhibitors (Bevacizumab, Apatinib) and immune checkpoint inhibitors (Pembrolizumab, Atezolizumab) have demonstrated promising anti-tumor effects. 374 In the case of DCIS, we are eagerly awaiting research on potential targets for anti-tumor effects specifically focused on the microenvironment.…”

Dysregulated Ribosome Biogenesis Is a Targetable Vulnerability in Triple-Negative Breast Cancer: MRPS27 as a Key Mediator of the Stemness-inhibitory Effect of Lovastatin

“…Despite the advances in breast cancer treatment, the prognosis for TNBC patients has seen little improvement over the past few decades 3 . Novel therapeutic strategies, including poly (ADP-ribose) polymerase (PARP) inhibition, immunotherapy, and inhibition of signaling pathways such as the androgen receptor, PI3K/AKT/mTOR, Notch, and EGFR pathways, are being actively explored 4 . Indeed, PARP inhibitors such as olaparib and veliparib 5 , immune checkpoint inhibitors such as pembrolizumab 6 , 7 , and antibody-drug conjugates (ADCs) such as sacituzumab govitecan 8 have demonstrated activity in a subset of TNBC patients.…”

“Triple-Punch” Strategy Exosome-Mimetic Nanovesicles for Triple Negative Breast Cancer Therapy

“…In recent years, the appreciation of TNBC has led to the development of targeted therapy and immunotherapy, including the application of PI3K/AKT/mTOR inhibitors, EGFR inhibitors, Notch inhibitors, PARP inhibitors, antibody-drug conjugates, and immune-checkpoint inhibitors. The revolutionizing therapeutic landscape provides the opportunities for advanced-stage disease and early stage TNBC patients. , Surgical adjuvant chemotherapy has been the main therapy for TNBC . However, due to the lack of chemotherapy-specific targeting, surgical adjuvant chemotherapy has difficulty removing all lesions, and the small number of remaining metastases will eventually lead to tumor relapse .…”