The development of new antitumor drugs depends mainly upon targeting tumor cells precisely. Trophoblast surface antigen 2 (Trop-2) is a type I transmembrane glycoprotein involved in Ca²⁺ signaling in tumor cells. It is highly expressed in various tumor tissues than in normal tissues and represents a novel and promising molecular target for caner targeted therapy. Up to now, the mechanisms and functions associated with Trop-2 have been extensively studied in a variety of solid tumors. According to these findings, Trop-2 plays an important role in cell proliferation, apoptosis, cell adhesion, epithelial-mesenchymal transition, as well as tumorigenesis and tumor progression. In addition, Trop-2 related drugs are also being developed widely. There are a number of Trop-2 related ADC drugs that have demonstrated potent antitumor activity and are currently been studied, such as Sacituzumab Govitecan (SG) and Datopotamab Deruxtecan (Dato-Dxd). In this study, we reviewed the progress of Trop-2 research in solid tumors. We also sorted out the composition and rationale of Trop-2 related drugs and summarized the related clinical trials. Finally, we discussed the current status of Trop-2 research and expanded our perspectives on its future research directions. Importantly, we found that Trop-2 targeted ADCs have great potential for combination with other antitumor therapies. Trop-2 targeted ADCs can reprogramme tumor microenvironment through multiple signaling pathways, ultimately activating antitumor immunity.

Breast cancer has accounted for the leading cause of cancer-related mortality among women worldwide. Although the progress in its diagnosis and treatment has come at a remarkable pace during the past several decades, there are still a wide array of problems regarding its progression, metastasis and treatment resistance that have not yet been fully clarified. Recently, an increasing number of studies have revealed that some members of Krüppel-like factors(KLFs) are significantly associated with cell proliferation, apoptosis, metastasis, cancer stem cell regulation and prognostic and predictive value for patients in breast cancer, indicating their promising prognostic and predictive potential for breast cancer survival and outcome. In this review, we will summarize our current knowledge of the functions, regulations and clinical relevance of KLFs in breast cancer.

Nectin-4 is a cell adhesion molecule which has gained more and more attention as a therapeutic target in cancer recently. Overexpression of Nectin-4 has been observed in various tumors, including breast cancer, and is associated with tumor progression. Enfortumab vedotin(EV)is an antibody-drug conjugate (ADC) targeting Nectin-4, which has been approved by FDA for the treatment of urothelial carcinoma. Notably, Nectin-4 was also investigated as a target for breast cancer in preclinical and clinical settings. Nectin-4-targeted approaches, such as ADCs, oncolytic viruses, photothermal therapy and immunotherapy, have shown promising results in early-phase clinical trials. These therapies offer novel strategies for delivering targeted treatments to Nectin-4-expressing cancer cells, enhancing treatment efficacy and minimizing off-target effects. In conclusion, this review aims to provide an overview of the latest advances in understanding the role of Nectin-4 in breast cancer and discuss the future development prospects of Nectin-4 targeted agents.

Circulating tumor cells (CTCs) play a critical role in the metastatic cascade and have emerged as promising biomarkers for cancer diagnosis, prognosis, and therapeutic monitoring. In breast cancer, CTCs mediate bone metastasis through intricate interactions with the bone microenvironment, regulating process such as homing, dormancy, reactivation, and colonization. Advances in CTC detection and characterization have deepened our understanding of their physical and biological properties, yet significant technical and biological challenges remain. This review provides a comprehensive overview of the roles of CTCs in breast cancer bone metastasis and highlighting their clinical significance, current limitations, and future applications.

As the first anti-HER2 targeted agent approved by FDA in 1998, Trastuzumab has significantly improved the outcome of patients with HER2 positive metastatic breast cancer. Unfortunately, resistance to trastuzumab is a severe obstacle to its therapeutic efficacy in clinical application, and its mechanism has not yet been fully elucidated. In our study, we found that stabilization of cyclin D3 could be one reason for trastuzumab resistance. Trastuzumab could induce G1/G0 phase arrest by downregulating cyclin D3 protein expression. However, the protein expression of cyclin D3 was not affected in trastuzumab-resistant cells, which might be related to aberrant activation of ERK signaling pathway. Furthermore, degradation of cyclin D3 protein by trastuzumab was mainly resulted from ubiquitin-dependent proteasome mechanism instead of transcriptional regulation. In trastuzumab-resistant breast cancer cells, trastuzumab-induced degradation of cyclin D3 protein was abrogated. When the ubiquitin pathway was inhibited, cells would show a predisposition to resistance to trastuzumab. Further, CDK4/6 inhibitor can inhibit the proliferation of trastuzumab-resistant HER-2 positive breast cancer cells. Therefore, combination of CDK4/6 inhibitors and anti-HER2 targeted therapy may be an alternative and promising strategy to overcome trastuzumab resistance in the future.

Background: Advanced triple-negative breast cancer (TNBC) has an extremely poor prognosis, and current therapies offer limited benefits for patients with low programmed cell death ligand 1(PD-L1) expression. This study innovatively proposes a “novel chemotherapy + bispecific antibody” model. Eribulin Mesylate (hereinafter referred to as Eribulin), a novel microtubule inhibitor, kills tumor cells while remodeling the tumor microenvironment. When combined with the PD-1/VEGF bispecific antibody Ivonescimab, it concurrently dismantles immunosuppression and angiogenesis to synergistically overcome immunotherapy resistance. Methods: This is a multicenter, open-label, single-arm clinical trial designed to enroll 29 patients with locally advanced or metastatic TNBC who have not received prior systemic anticancer therapy, and who are either ineligible for radical surgical resection or local therapy, or have experienced disease progression following postoperative adjuvant therapy. The primary endpoint is the objective response rate (ORR) assessed by Investigator Assessment (INV) at each participating center based on strict adherence to Response Evaluation Criteria in Solid Tumors version 1.1(RECIST v1.1) criteria. Secondary endpoints include progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. Exploratory endpoints involve potential biomarkers, the correlation between PD-L1 expression and efficacy, and patient-reported outcomes (PROs). Discussion: This combination regimen is expected to leverage the synergistic advantages of “chemotherapy-promoted immunity and potent bispecific antibody efficacy,” providing novel evidence-based medical evidence for the first-line treatment of metastatic TNBC and thereby effectively addressing significant unmet clinical needs. Clinical Trial Registration: http://www.chictr.org.cn/ , identifier ChiCTR2600117652.