Breast cancer is the second cancer-related cause of death in women worldwide, therefore it is no surprise breast cancer sits second in top disease of worldwide pipeline drugs, highlighting the global effort to counter its burden. Behind these efforts stands academic, biotechnology and pharmaceutical stakeholders that drive innovation toward better care of patients.
In this article, we highlight these efforts and focus on the breast cancer trends in research and pharma from July and August 2025. First, we explore cutting-edge research directions, including breast cancer organoids, breast cancer-on-chip platforms, and 3D in vitro models that serve as new approach methodologies (NAMs) to better understand tumor biology and resistance. Second, we review industry updates: regulatory milestones, clinical trial progress, and new targeted therapies shaping breast cancer drug discovery.
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Academic Research Trends
The use of NAMs is transforming breast cancer research by offering human-relevant, animal-free systems that better replicate the complexity of tumors. Organoids, breast cancer-on-chip platforms, and advanced 3D in vitro models allow scientists to study tumor biology, drug response, and resistance mechanisms with unprecedented fidelity. These systems are increasingly viewed by the pharmaceutical industry as essential translational tools, bridging basic research and clinical application supported by regulatory pushes such as the FDA’s Modernization Act III.. Through a PubMed-based retrieval and analysis of recent publications, we identified three dominant academic trends that are shaping the field: AI/omics biomarkers, immuno-TME research, and DNA damage/PARP biology.
AI, Omics & Biomarkers
A major trend in breast cancer research is the integration of artificial intelligence (AI), multi-omics, and biomarker discovery with NAMs such as breast cancer organoids and breast cancer-on-chip platforms. The FDA has already recognized AI/ML and omics, in combination with advanced 3D in vitro models, as tools capable of generating regulatory-relevant data for IND submissions. Academic research is rapidly adopting this trio to map resistance, stratify patients, and identify new therapeutic opportunities.
Sun et al. (Gut) used single-cell and spatial transcriptomics in breast cancer 3D organoid models to profile cancer-associated fibroblasts, defining an endothelial-like CAF state that drives angiogenesis and invasion. This omics approach also revealed stromal programs that may serve as biomarkers for disease aggressiveness. In parallel, Jiang et al. (Nature Communication) applied AI-driven virtual screening and modeling to identify Bufalin as a molecular glue degrader of estrogen receptor alpha, then validated its effect in breast cancer organoids, highlighting how AI can accelerate discovery of next-generation ER-targeting therapies. Extending biomarker applications, Zhang et al. combined multi-omics profiling with exosome–tumor–vascular co-cultures in organoid systems, uncovering molecular signatures linked to vascular remodeling and therapeutic resistance.
Immunotherapy & Tumor Microenvironment
Immunotherapy continues to dominate breast cancer research, yet its success is often limited by resistance mechanisms rooted in the tumor microenvironment (TME). Stromal cells, immune infiltrates, and the extracellular matrix (ECM) all contribute to immune evasion, epithelial–mesenchymal transition (EMT), and metastatic spread. Incorporating these components into advanced 3D in vitro models such as breast cancer organoids and breast cancer-on-chip systems provides new opportunities to understand how the TME shapes treatment outcomes.
For instance, Chen et al. (Biomaterials, 2025) designed multimodal cascade-amplified phototheranostics in breast cancer organoid models, showing that photodynamic therapy can synergize with immune checkpoint blockade to induce immunogenic cell death. Piwocka et al. (Scientific Reports) introduced tetraculture spheroids integrating tumor, stromal, endothelial, and immune cells, a personalized 3D breast cancer model where responses to immunotherapy could be assessed in the presence of a complex TME. Pezeshki et al. (Scientific Reports) explored patient-derived scaffolds to replicate the ECM, demonstrating that ECM stiffness and composition directly enhance invasive gene programs, influencing metastasis and resistance to immune-based therapies.
DNA Damage, HRD & PARP Biology
The DNA damage response remains a cornerstone of breast cancer research, with particular focus on homologous recombination deficiency (HRD) and therapeutic strategies involving PARP inhibitors. By integrating these pathways into NAMs, investigators are gaining deeper insights into how genomic instability and microenvironmental cues influence therapy response.
Jones et al. (Scientific Reports, 2025) demonstrated how matrix stiffness alters aldehyde dehydrogenase activity and DNA damage signaling in breast cancer organoids, showing that physical properties of the microenvironment can reprogram DNA repair dynamics and potentially modulate sensitivity to DNA-targeting drugs. Oliveira et al. (Cancer Research, 2025) explored epigenetic heritability of cell plasticity, revealing that transcriptional reprogramming in breast cancer organoids drives the emergence of HRD-like states, providing a mechanistic link between plasticity and genomic instability. Adding a therapeutic perspective, Khoury et al. (Journal of Controlled Release, 2025) developed radiation-guided nanoparticles combined with PARP inhibitors in breast cancer spheroids, enhancing immunotherapy efficacy by exploiting DNA repair vulnerabilities and promoting immunogenic cell death.
Pharma & Biotech News
In parallel with academic advances, the pharmaceutical and biotechnology sectors announced several important updates in breast cancer drug development over July and August 2025. These span targeted therapies, immuno-oncology, and novel modalities, reflecting how the field continues to diversify beyond endocrine therapy and chemotherapy. Regulatory filings and trial progress emphasize how new candidates are moving closer to clinical practice.
Datopotamab deruxtecan (Dato-DXd, Daiichi Sankyo/AstraZeneca) advanced in hormone receptor–positive/HER2-low breast cancer, with the companies announcing the initiation of a Phase III registrational trial after positive Phase II readouts earlier in the year. This ADC, which targets TROP2, is being closely watched as a potential successor to sacituzumab govitecan, and the July update marked a key step toward broader regulatory submission strategies.
Patritumab deruxtecan (HER3-DXd, Daiichi Sankyo/AstraZeneca) also moved forward, with regulators in the U.S. and EU accepting updated IND amendments for expanded evaluation in HER3-expressing metastatic breast cancer. The inclusion of breast cancer as a major indication underlines the industry’s growing focus on HER3 as an actionable target.
In the immuno-oncology space, Merck and Moderna announced that their personalized mRNA cancer vaccine (mRNA-4157), already in evaluation in melanoma, entered a Phase II trial in triple-negative breast cancer (TNBC) in August. The trial will test the vaccine in combination with pembrolizumab, representing one of the first significant moves to bring individualized mRNA vaccines into the breast cancer landscape.
From a novel modality perspective, CureVac reported that its siRNA-based therapeutic targeting ESR1 mutations received FDA clearance for Phase I initiation in metastatic endocrine-resistant breast cancer. The IND approval in July highlights how RNA-based drugs are entering niches once dominated by small molecules like SERDs.
Gilead and Arcus Biosciences announced progress with their TIGIT inhibitor domvanalimab in combination with anti-PD-1 therapy, moving into a Phase II breast cancer expansion cohort. Although TIGIT programs have seen mixed results in other tumor types, the decision to expand into breast cancer reflects continued investment in novel checkpoint strategies.
Finally, Shanghai-based Zai Lab disclosed in August that its PARP1-selective inhibitor (ZL-817) received China NMPA clearance for Phase I/II testing in BRCA-mutant breast cancer. This adds to a global push toward next-generation PARP inhibitors designed to improve efficacy while reducing hematologic toxicity.
