Evolution and future directions of bispecific antibodies in breast cancer: a global clinical trial landscape analysis

Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.

Immunotherapeutic strategies for castration-resistant prostate cancer: A systematic review of mechanisms, clinical advances and emerging approaches

Unraveling the use of vaccine therapy in HER-2 positive breast cancer: a comprehensive review of current state and future perspectives

Despite significant advances in early detection and therapeutic strategies, breast cancer (BC) continues to pose a major public health challenge. The treatment of HER2-positive (HER2 +) BC has evolved substantially over recent years with the advent of monoclonal antibodies (mAbs), small-molecule tyrosine kinase inhibitors (TKIs), and antibody–drug conjugates (ADCs). Clinical progress has been significantly accelerated by a deeper understanding of the immune-regulatory properties of this subtype and its interactions with the tumor microenvironment. Despite the availability of effective HER2-targeted therapies, approximately one-third of patients develops resistance, highlighting the need for novel and more durable treatment strategies. Indeed, while current treatments have shown promising efficacy by promoting a “passive immune response,” they are associated with the emergence of resistant clones. Conversely, vaccine-based therapies are designed to elicit a durable “active immune response” by presenting tumor-associated antigens that stimulate the host immune system to recognize and eliminate malignant cells. This approach has the potential to generate long-lasting immunological memory, preventing recurrence, disease progression, and the emergence of immune-evasive tumor variants. This review provides a comprehensive overview of cancer vaccines strategies for HER2 + BC with emphasis on their mechanisms, advantages, limitations, and their current developmental status. We explore diverse delivery platforms, including peptide/protein-based, nucleic acid, and cell-based vaccines. The clinical utility of these strategies is assessed across different disease settings: from prevention and interception in pre-invasive lesions, to the (neo)adjuvant treatment of early-stage BC and the management of advanced metastatic disease. While advanced-stage BC often presents an immunosuppressive tumor microenvironment that hinders vaccine efficacy, early-stage disease offers a more favorable immunological milieu for inducing robust and durable T-cell responses. Furthermore, we discuss emerging innovations such as neoantigen discovery, next-generation adjuvants (e.g., TLR and STING agonists), and novel combinatorial approaches with checkpoint inhibitors to overcome immune evasion. Although most BC vaccines remain under clinical investigation, they represent a promising frontier for achieving disease control and the coming decade is expected to yield pivotal insights into their clinical utility and therapeutic potential.

Harnessing immunity against breast cancer: from checkpoints to cell therapies

Breast cancer (BC) remains the leading cause of cancer-related mortality and a major contributor to disease burden among women worldwide. Although PD‑1/PD‑L1‑targeting immune checkpoint inhibitors have become a standard treatment for certain triple‑negative breast cancer subgroups, their use across the broader BC population is limited by intrinsic resistance, an immunosuppressive tumor microenvironment (TME), and treatment‑related adverse effects. The present review offers a comprehensive synthesis of the immunotherapeutic paradigm in BC, spanning ICIs, adoptive cellular therapies (CAR-T, CAR-NK, CAR-M, TIL, TCR-T, and CIK cells), and emerging immune modulators. We critically evaluate pivotal clinical trials, discuss cross-cutting challenges—including biomarker development, therapy resistance, and the practical limitations of cellular products—and highlight rational combinatorial strategies. By contrasting the translational readiness of diverse modalities and outlining a framework for personalized therapy, this review aims to inform future research and clinical practice in harnessing immunity against BC.

Developing next-generation antibody-drug conjugates for breast cancer drug delivery: hurdles and advances in the clinic.

This review synthesizes literature spanning 1990-2026 on advances in ADC design and their clinical and translational implementation in breast cancer to support reframing antigen selection as a system-level challenge, supported by delivery-focused engineering, precision-medicine-driven trial design, and adaptive methodology.

Datopotamab deruxtecan in breast cancer treatment: a systematic review of clinical efficacy and safety

Breast cancer (BC) remains the most common malignant tumor in women worldwide and a leading cause of cancer-related deaths. Despite therapeutic advances, patients with advanced BC, particularly triple-negative breast cancer (TNBC), still face limited effective treatment options. Antibody-drug conjugates (ADCs) represent a compelling strategy that combines precise tumor targeting with cytotoxic payloads, effectively bridging targeted delivery with microenvironmental disruption. Datopotamab deruxtecan (Dato-DXd), a Trop-2-targeted ADC, has demonstrated encouraging clinical activity. Preclinical evidence suggests that Dato-DXd may modulate the tumor microenvironment (TME) through potential induction of immunogenic cell death (ICD), providing a biological rationale for investigating synergistic combinations with immunotherapy. A systematic review was conducted in accordance with PRISMA guidelines using the PubMed, Web of Science, and ClinicalTrials databases. The inclusion criteria targeted relevant clinical studies published between 2024 and 2026. Ultimately, after a thorough analysis, one randomized controlled trial (RCT) and one single-arm study met the eligibility criteria and were included in the review. Data analysis from the Phase III TROPION-Breast01 trial demonstrated that Dato-DXd significantly improved objective response rate (ORR) and median progression-free survival (PFS) compared to investigator’s choice chemotherapy in patients with HR+/HER2- breast cancer. In the Phase I TROPION-PanTumor01 trial, Dato-DXd showed promising clinical activity in both HR+/HER2- breast cancer and TNBC cohorts. Regarding safety, Dato-DXd was associated with a lower incidence of grade ≥ 3 adverse events compared to standard chemotherapy in the randomized setting, although low-grade toxicities such as stomatitis and nausea remained common. Dato-DXd demonstrates robust clinical activity in patients with BC, providing superior disease control with a favorable safety profile compared to conventional chemotherapy. Beyond direct tumor cell ablation, its mechanism of action includes a potent bystander killing effect, while preclinical data suggest that the induction of ICD may contribute to reshaping a heterogeneous TME. Future research is needed to correlate these preclinical mechanistic hypotheses with clinical outcomes. The limited number of available RCTs and Real-World Evidence (RWE) studies underscores the need to raise awareness and conduct further research to identify predictive biomarkers and evaluate combinations with immune checkpoint inhibitors to optimize personalized treatment regimens. https://www.crd.york.ac.uk/prospero/ , identifier CRD420261408796.