Search Results (1,234)

Background/Objectives: Epithelial ovarian cancer (EOC) remains a gynecologic malignancy with a poor prognosis, with a 5-year survival of approximately 29% in advanced-stage disease. Despite cytoreductive surgery and platinum- and taxane-based chemotherapy, most patients relapse within 2 years. Major therapeutic barriers include chemoresistance, molecular heterogeneity, and an immunosuppressive peritoneal microenvironment. This review summarizes emerging therapeutic strategies for EOC, their mechanisms of action, and their potential to overcome treatment resistance. Methods: PubMed/MEDLINE was searched for preclinical studies, phase I–III clinical trials, systematic reviews, and meta-analyses addressing novel ovarian cancer therapies and resistance mechanisms. Results: The review covers molecularly targeted therapies, immunotherapies, metabolic and epigenetic approaches, cellular and gene therapies, targeted drug-delivery systems, and locoregional and physical modalities. Strategies include PARP inhibitors, antiangiogenic agents, antibody–drug conjugates, pathway inhibitors, immune checkpoint inhibitors, cancer vaccines, adoptive cell therapies, metabolic and epigenetic modulators, CAR-T, CAR-NK, CRISPR/Cas9, HIPEC, PIPAC, ablation, photodynamic therapy, and sonodynamic therapy. Conclusions: The clinical maturity of these approaches varies substantially. PARP inhibitors, antiangiogenic agents, selected antibody–drug conjugates, MAPK-directed therapy in LGSOC, and HIPEC in selected settings have the strongest clinical support. Most immune combinations, metabolic and epigenetic therapies, adoptive cell therapies, gene-editing approaches, and novel delivery or physical modalities remain early clinical or predominantly preclinical. Progress will depend on biomarker-guided patient selection, reassessment of evolving resistance mechanisms, and rational treatment sequencing and combinations. Full article

Antibody–drug conjugates (ADCs) targeting HER2 (encoded by ERBB2), Trop2 (TACSTD2), and Nectin-4 (NECTIN4) have demonstrated clinical activity in bladder cancer. However, the co-expression relationships among these three targets at both the transcriptomic and protein levels, and their spatial organization within the tumor microenvironment, remain incompletely characterized. To address this, we performed a multi-platform, multi-resolution analysis integrating ten bulk RNA-seq datasets (n = 1628 samples), six spatial transcriptomics datasets (10x Visium and Visium HD, n = 31 specimens), and multiplex immunofluorescence (mIF) staining on three paired tumor–adjacent normal bladder specimens. Pairwise Pearson correlation analyses were conducted for ERBB2, TACSTD2, and NECTIN4 across bulk transcriptomes and spatial compartments (tumor core, interface, and stroma). High-resolution co-expression hotspot mapping was performed using Visium HD data. Preliminary protein-level evidence was obtained using mIF, with quantitative three-dimensional surface plot reconstructions illustrating the spatial distribution of marker co-expression. Given the limited number of specimens (three paired tumor–normal samples), these findings should be regarded as exploratory and illustrative rather than definitive validation. Moderate-to-strong positive correlations among the three genes were consistently observed across all ten bulk datasets, with the strongest association between TACSTD2 and NECTIN4 (Pearson r up to 0.969). Spatial transcriptomic analyses recapitulated these positive correlations across all histopathological compartments, with the tumor core generally exhibiting the highest coefficients. No consistent spatial gradient was observed, indicating preservation of co-expression across tissue niches. Visium HD analysis confirmed positive pairwise correlations and identified discrete co-expression hotspots. mIF revealed extensive Trop2–Nectin-4 protein colocalization across all tumors, whereas HER2 showed more restricted and heterogeneous expression. Triple-positive subpopulations were identified but were limited. Strikingly, all three markers exhibited pronounced tumor-specific upregulation relative to paired adjacent normal tissues, with surface plot analysis showing markedly elevated cumulative fluorescence intensities in tumors (Z-values approaching 240 arbitrary units) compared with a flattened landscape in normal tissues (Z-values < 100–120 arbitrary units). These findings provide a multi-scale description of ADC-target co-expression in bladder cancer and generate hypotheses for biomarker-driven patient stratification, which require validation in larger, independent cohorts. Full article

Integrins are heterodimeric transmembrane receptors that mediate bidirectional signaling and regulate cell–cell and cell–extracellular matrix interactions. Integrin αvβ6 is an epithelial-associated integrin that has emerged as a promising molecular target for PET/CT imaging using integrin αvβ6-directed radiotracers such as ⁶⁸Ga-Trivehexin, and, most recently, for antibody–drug conjugate therapy in epithelial malignancies. Unexpected physiological and incidental uptake within the pituitary gland has been reported in integrin αvβ6-targeted PET studies, including uptake in morphologically normal pituitary glands and pituitary neuroendocrine tumors (PitNETs). However, the histological basis of integrin αvβ6 expression in the human pituitary gland remains poorly understood. The aim of this study is to characterize the immunohistochemical expression of integrin αvβ6 in normal human pituitary tissue and PitNETs and to evaluate its potential implications for integrin αvβ6-targeted imaging and theranostic applications. Five complete adult pituitary glands obtained at autopsy and 28 PitNETs were examined by immunohistochemistry for integrin αvβ6. Staining distribution, intensity, and cellular localization were assessed in the adenohypophysis, neurohypophysis, and Rathke’s cleft remnants. PitNETs were classified according to transcription factor expression (PIT1, TPIT, and SF1). Among the 28 PitNETs, 17 were SF1-lineage (60.7%), three were PIT1-lineage (10.7), two were TPIT-lineage (7.1%), three lacked a dominant transcription factor (10.7%), and three showed plurilineage expression (10.7%). Integrin αvβ6 expression was evaluated semiquantitatively according to staining intensity and the percentage of positive tumor cells. In normal pituitary glands, integrin αvβ6 immunoreactivity was predominantly membranous and localized to larger adenohypophyseal cells irrespective of transcription factor lineage or hormone phenotype. Strong expression was also observed in the epithelial lining cells of Rathke’s cleft remnants, whereas the neurohypophysis lacked detectable integrin αvβ6 expression. Among the 28 PitNETs, integrin αvβ6 expression was detected in 20 cases (71.4%). Positive tumors demonstrated variable staining intensity and extent, ranging from 20% to 100% positive tumor cells. By lineage, integrin αvβ6 expression was detected in 13 of 17 SF1-lineage tumors (76.5%), one of three PIT1-lineage tumors (33.3%), and zero of two TPIT-lineage tumors (0%). Additionally, all three tumors lacking a dominant transcription factor (100%) and all three plurilineage tumors (100%) demonstrated integrin αvβ6 expression. Eleven integrin αvβ6-positive tumors showed expression in ≥50% of tumor cells, and six exhibited strong or diffuse immunoreactivity. Integrin αvβ6 expression in adenohypophyseal cells and Rathke’s cleft remnants provides a histological explanation for physiological pituitary uptake observed on αvβ6-targeted PET/CT imaging. The high prevalence of integrin αvβ6 expression in PitNETs, particularly in a subset demonstrating strong and diffuse immunoreactivity, suggests potential applicability of integrin αvβ6-targeted molecular imaging and theranostic approaches, including both radioligand- and antibody-based strategies. However, these applications remain investigational and require further validation in preclinical and clinical studies. At the same time, physiological integrin αvβ6 expression in normal anterior pituitary tissue may limit imaging specificity and should be considered when developing integrin αvβ6-targeted radioligand therapies. Further clinicopathological and imaging correlation studies are warranted to define the diagnostic and therapeutic role of integrin αvβ6-targeted approaches in PitNETs. Full article

Background: Extramammary Paget disease (EMPD) is a rare epithelial malignancy that arises in the apocrine gland-bearing skin. Although localized intraepidermal EMPD generally follows an indolent clinical course, invasive EMPD is associated with lymph node metastasis, distant dissemination, and poor survival. Owing to its rarity, high-level evidence is limited and treatment strategies remain incompletely standardized, particularly for advanced disease. Recent advances in molecular profiling have revealed actionable therapeutic targets and created new opportunities for precision medicine. Methods: A narrative review was conducted using the PubMed database through May 2026. Relevant literature regarding the epidemiology, prognostic factors, surgical and non-surgical management, lymph node management, radiotherapy, systemic therapies, molecularly targeted therapies, and future therapeutic directions for EMPD is reviewed and summarized. Results: Surgical excision remains the standard treatment for resectable localized EMPD. Margin-controlled approaches, including Mohs micrographic surgery, complete circumferential peripheral and deep margin assessments, and mapping biopsy-guided excision, have contributed to improved local disease control. Radiotherapy, topical imiquimod, and photodynamic therapy provide alternative treatment options for patients who are unsuitable candidates for surgery; however, recurrence remains a major challenge. The management of regional lymph node metastases includes sentinel lymph node biopsy, lymph node dissection, and adjuvant radiotherapy in selected patients. For metastatic disease, conventional chemotherapy based on taxanes and fluoropyrimidine/platinum combinations has demonstrated moderate antitumor activity but limited durability. Molecular characterization of EMPD has identified several promising therapeutic targets. HER2 overexpression or amplification, observed in approximately 30–40% of cases, has emerged as the most clinically validated biomarker, with trastuzumab-based therapies demonstrating substantial efficacy. Immune checkpoint inhibitors have shown activity in selected patients, particularly those with a high tumor mutational burden, although predictive biomarkers remain inadequately defined. Additional emerging targets include androgen receptor signaling, TROP2, NECTIN4, FOXM1, and PIK3CA-associated pathways. Conclusions: In addition to conventional surgery- and chemotherapy-based approaches, biomarker-driven precision oncology is gaining attention as a treatment strategy for EMPD. HER2-targeted therapies, antibody–drug conjugates, and rationally selected immunotherapeutic strategies are expected to play increasingly important roles in the treatment of advanced disease. Continued translational research, international collaboration, and prospective clinical trials are essential to establish evidence-based treatment algorithms and improve outcomes in patients with this rare but potentially aggressive malignancy. Full article

Primary bone sarcomas are rare, heterogeneous malignancies with limited therapeutic options, particularly in metastatic disease where outcomes remain poor. This study synthesizes current literature to evaluate emerging therapeutic strategies and biological determinants of response across osteosarcoma, Ewing sarcoma, and chondrosarcoma, as presented at the ESMO Annual Meeting, 2025. Key approaches reviewed include VEGFR-targeted tyrosine kinase inhibitors (TKIs), DNA damage response (DDR) inhibition, MYC targeting, immune checkpoint inhibitors (ICIs), and surfaceome-directed therapies such as antibody–drug conjugates (ADCs) and chimeric antigen receptor T cell therapy. Across studies, TKIs demonstrated short lasting activity as monotherapy but improved outcomes in some of the studies when combined with ICIs or chemotherapy, reflecting their role in remodeling the tumor microenvironment (TME); importantly, controlled studies with TKI and chemotherapy upfront are ongoing. DDR- and MYC-targeted therapies have shown strong preclinical rationale but limited clinical efficacy, highlighting challenges in translation. Immune-based therapies exhibited variable responses, with dedifferentiated chondrosarcoma (DDCS) emerging as a responsive histotype. Surfaceome-targeting strategies, particularly ADCs, demonstrated promising early clinical activity. Overall, bone sarcoma rarity, tumor heterogeneity, immunosuppressive TME, and lack of predictive factors challenge drug discovery for bone sarcoma patients. These findings underscore the importance of combination strategies and biomarker-driven patient selection and suggest that continued integration of targeted and immunotherapeutic approaches will be critical to improving outcomes in bone sarcoma. Full article

Background/Objectives: Antibody–drug conjugates (ADCs) targeting Nectin-4 (enfortumab vedotin) and TROP-2 (sacituzumab govitecan) have transformed the management of advanced urothelial carcinoma (UC), but evidence on their molecular targets in rare non-urothelial bladder carcinomas (N-UC) is scarce. We evaluated the immunohistochemical expression of TROP-2 and Nectin-4 in muscle-invasive UC and N-UC and assessed their association with tumour stage, nodal status and overall survival. Methods: In this retrospective single-centre study, 111 consecutive patients with primary muscle-invasive bladder carcinoma (73 UC, 38 N-UC including squamous, adenocarcinoma, neuroendocrine and sarcomatoid variants) were analysed. TROP-2 and Nectin-4 expression was quantified using the H-score; positivity was defined as ≥15. Marker expression was correlated with clinicopathological characteristics and overall survival (OS) using chi-squared, linear-by-linear, log-rank, and Cox regression analyses. Results: TROP-2 positivity was observed in 46.6% of UC and 36.8% of N-UC (p = 0.925); Nectin-4 positivity in 17.8% and 28.9%, respectively (p = 0.275). Among positive cases, TROP-2 H-scores were higher in N-UC than in UC (mean 109 vs. 70; Mann–Whitney p = 0.045; Cliff’s delta 0.37, 95% CI 0.05–0.66); as no adjustment for multiple testing was applied, this difference is regarded as nominally significant and exploratory. Nectin-4 H-scores were numerically higher in UC (mean 82 vs. 53) but did not reach statistical significance (p = 0.84). Across the cohort, TROP-2 expression increased with advancing T stage (linear-by-linear p = 0.026) and was associated with nodal involvement (p = 0.043). Nectin-4 showed no significant stage association. Sarcomatoid carcinomas were negative for both markers. Median OS was 41 months in UC versus 19 months in N-UC (p = 0.668). Neither marker independently predicted OS, whereas advanced T stage (p = 0.003) and nodal involvement (p = 0.021) were significantly associated with poorer survival; T stage remained independently prognostic in multivariable analysis. Conclusions: TROP-2 and Nectin-4 are expressed at comparable rates in muscle-invasive UC and rare N-UC, except in sarcomatoid variants. TROP-2 expression increased with advancing tumour stage, suggesting stage-dependent regulation in muscle-invasive disease. Therefore, both markers should be interpreted as potential therapeutic targets whose expression can be demonstrated in these tumours, rather than as prognostic biomarkers or as validated predictive biomarkers of ADC response; because no patient received an ADC, the present study cannot determine whether expression predicts clinical benefit, and this distinction requires prospective, treatment-linked evaluation that includes patients with N-UC. Full article

Peptides have attracted increasing popularity in modern drug discovery, with the potential to address unmet clinical needs that lie beyond the reach of small molecules and antibodies. By offering “best-of-both-worlds” features, peptides are emerging as powerful tools for targeting disease-associated, challenging proteins. Combinatorial peptide libraries have played a crucial role in the development of peptide drugs. Phage display is one of the most widely adopted combinatorial frameworks for pharmaceutical exploration, ushering in a new paradigm in peptide drug discovery over the past few decades. Phage display libraries provide a vast repertoire of ligands that can be searched through biopanning to identify peptides with high specificity and affinity for a diverse range of biologically relevant targets. Although biopanning has demonstrated great potential in identifying target-specific ligands, many peptides identified by phage display still suffer from poor pharmacological properties, creating hurdles in translating initial hits from phage display selections into therapeutic molecules. To achieve improved pharmacological characteristics, various modifications can be introduced into peptides, such as cyclization, the incorporation of non-canonical amino acids, the introduction of D-amino acids, oligomerization, conjugation/fusion, and stapling. Optimizing peptide properties through these strategies has laid a solid groundwork for a significant number of phage display-derived peptides to progress from fundamental research and preclinical studies into various phases of clinical evaluations, with several peptide drugs already receiving regulatory approval for routine clinical applications. These achievements raise hopes for peptide phage display to remain a promising platform for drug discovery in the years ahead. Full article

Background: Antibody-drug conjugates (ADCs) are gaining rapidly expanding clinical utility, with a growing number of approved indications across compounds that differ in target antigen, payload mechanism, and linker design. However, treatment response remains heterogeneous, and predictive biomarkers to identify patients most likely to benefit are limited. Given that ADC efficacy depends on sufficient target antigen expression and distribution across tumor lesions, positron emission tomography (PET) imaging offers a unique opportunity to non-invasively assess whole-body target availability. We therefore conducted a systematic literature review to evaluate the relationship between PET-measured tumor antigen expression and the therapeutic response to ADCs targeting the same antigen. Method: A systematic comprehensive search of PubMed, EMBASE and Web of Science databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, using terms related to targeted PET, ADC treatment and response assessment. Article screening, eligibility assessment, and data extraction were performed independently using predefined criteria by two reviewers. Disagreements were resolved by consensus. Results: A total of 5628 records were identified. After removing duplicates, 4323 records were screened by title and abstract. Fifty-eight underwent full-text review and seven were included in the final review. Four trials investigated human epidermal growth factor receptor 2 (HER2)-targeted therapy, one Nectin-4, one mesothelin and one STEAP1. In all HER2- and Nectin-4-related trials, patients with a higher uptake on targeted PET had a higher probability of responding to targeted treatment. Included trials were generally small and had a moderate risk of bias. Conclusion: Targeted PET imaging showed potential to predict treatment response in trials evaluating clinically active agents. Additional clinical trials across a broader range of targets, along with standardized acquisition protocols and harmonized study designs, are needed to enable the integration of this technique into clinical practice and ultimately translate its benefits to patients. Full article

Monoclonal antibodies are emerging as advanced therapies in companion-animal medicine, with approved or clinically evaluated applications in canine and feline osteoarthritis pain, canine atopic dermatitis, and selected infectious-disease and oncological settings. This critical narrative review integrates peer-reviewed studies, regulatory records, product information, and publicly available therapeutic-antibody sequence resources to examine target biology, species adaptation, Fc function, developability, and clinical implementation. Anti-NGF and anti-IL-31 products demonstrate the clinical value of long dosing intervals, whereas oncology and infectious-disease programmes remain subject to indication-specific efficacy and safety requirements. Canine and feline IgG subclasses, Fc-receptor and FcRn biology, incomplete feline framework resources, manufacturing economics, and owner-funded care all influence candidate design and deployment. Emerging bispecific antibodies, antibody–drug conjugates, VHHs, mRNA-based approaches, and AI-assisted strategies are most relevant when they address a defined veterinary use case. We propose a translational framework linking target validation, species-adapted engineering, species-matched assays, manufacturability, regulatory evidence, and real-world deployment. Full article

Antibody–drug conjugates (ADCs) have emerged as a powerful class of targeted therapeutics in many clinical areas, such as in oncology. Despite their efficacy, the onset of adverse events has been a major drawback in their clinical use. Among other explanations, the clinical performance of the ADCs has been associated with the chemistry of the linker connecting the antibody and payload. Linkers determine plasma stability, intracellular activation, and payload diffusibility, thereby influencing the therapeutic index, off-tumour toxicity, and by-stander activity. Mechanistic insights increasingly show that linker–payload properties govern catabolite permeability and intratumoral distribution, particularly in antigen-heterogeneous settings. Current developments include enzyme-cleavable and tumour-selective linkers, polarity-modulating masking strategies, alternative self-immolative spacers, and dual-trigger systems designed to enhance selectivity and decouple efficacy from toxicity. In parallel, linker behaviour intersects with broader mechanisms of tumour resistance. This review focuses on understanding these processes, which are essential for designing the next generation of linkers capable of improving stability, safety, and long-term therapeutic effectiveness across diverse tumour contexts. Full article

Background/Objectives: Cutaneous adverse events (cAEs) are among the most common toxicities associated with modern anticancer therapies and can significantly affect quality of life, treatment adherence, and therapeutic outcomes. This narrative review aims to provide an updated overview of the mechanisms, clinical manifestations, prognostic implications, and management strategies of cancer therapy-related cutaneous toxicities, with a particular focus on precision oncodermatology. Methods: A narrative review of the recent literature was performed, integrating evidence from clinical studies, meta-analyses, pharmacovigilance investigations, consensus guidelines, and translational research. The review examines cutaneous toxicities associated with immune checkpoint inhibitors, targeted therapies, antibody–drug conjugates, and other emerging anticancer treatments. Results: Four major axes were identified: immune disinhibition, epithelial signaling inhibition, cytotoxic epithelial injury, and cytokine-driven immune activation. Cutaneous immune-related adverse events (cirAEs) emerged as potential biomarkers of treatment efficacy, particularly vitiligo, lichenoid, and psoriasiform eruptions. Increasing evidence supports the use of steroid-sparing biologic therapies, including dupilumab, omalizumab, anti-IL-17 agents, and Janus kinase inhibitors, although prospective validation remains limited. Recent advances in immunologic endotyping have identified distinct inflammatory pathways that may enable personalized therapeutic approaches. Antibody–drug conjugates represent an expanding source of unique dermatologic toxicities requiring dedicated management strategies. Emerging biomarkers, including cytokine signatures and microRNAs, may further refine risk stratification and treatment selection. Conclusions: The management of cancer therapy-related cutaneous toxicities is evolving toward a precision medicine model integrating clinical phenotype, immunologic endotype, and biomarker profiling. Early multidisciplinary intervention and mechanism-based therapeutic strategies may improve patient outcomes while preserving anticancer efficacy. Prospective studies are needed to validate biomarker-guided and steroid-sparing approaches in oncodermatology. Full article

Background/Objectives: Small-cell lung cancer (SCLC) remains one of the most therapeutically challenging malignancies despite recent advances in chemoimmunotherapy. Although platinum–etoposide combined with programmed death ligand 1 (PD-L1) blockade has modestly improved survival in extensive-stage disease, most patients ultimately develop treatment resistance. This review examines the evolving biological basis of therapeutic resistance and discusses how emerging treatment strategies may be integrated into biologically informed clinical development. Methods: We conducted a narrative review of recent translational studies, clinical trials, regulatory updates, and major oncology meeting presentations addressing emerging therapeutic strategies, biomarkers, and adaptive resistance mechanisms in SCLC. Results: Advances in molecular profiling have established that SCLC comprises dynamically evolving transcriptional states characterized by lineage plasticity, replication-stress dependency, immune suppression, and antigen remodeling. These biological insights have accelerated the development of delta-like ligand 3 (DLL3)-directed immune-redirection strategies, next-generation antibody–drug conjugates, DNA damage response-targeting therapies, and epigenetic approaches. Across these platforms, however, clinical translation remains constrained by antigen heterogeneity, biomarker instability, lineage plasticity, immune dysfunction, and cumulative toxicity. We organize the available evidence across three clinically relevant treatment windows—induction, post-induction residual disease, and relapse—to clarify how therapeutic timing may influence the role and expected clinical performance of each strategy. Conclusions: Future clinical development should prioritize the prospective validation of dynamic biomarkers and treatment strategies tailored to specific disease stages. Such an approach may improve patient selection, guide therapeutic sequencing, and increase the durability of treatment benefit in extensive-stage SCLC. Full article

The epidermal growth factor receptor (EGFR) was the first receptor tyrosine kinase identified soon after v-Src was recognized as a tyrosine kinase. EGFR signaling begins when EGF binds to EGFR at the cell surface, inducing receptor dimerization, activation, and autophosphorylation. The resulting phosphotyrosine sites recruit downstream effectors that activate signaling cascades such as the RAS-RAF-MEK-ERK and PI3K-Akt pathways, thereby regulating cell growth, proliferation, and survival. EGF binding also promotes EGFR endocytosis, which can direct the receptor to lysosomal degradation. Aberrant EGFR activity is associated with many cancers, and the receptor has been therapeutically targeted using small-molecule tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs). Furthermore, EGFR endocytosis has been exploited for the targeted delivery of anticancer agents into EGFR-expressing cancer cells through antibody–drug conjugates (ADCs) and antibody–nanoparticle conjugates (ANCs). Although ADCs and ANCs both utilize mAbs as homing mechanisms to recognize cancer-associated antigens, they further harness EGFR endocytosis to deliver therapeutic payloads directly into target cells. In this review, we briefly discuss EGFR structure, activation, signaling, and endocytosis, as well as the mechanisms underlying EGFR function in cancer development. We then focus on current advances and future perspectives in using EGFR endocytosis pathways to improve targeted cancer drug delivery and therapy, particularly in the context of ANCs. Full article

Background: Next-generation sequencing (NGS)-detected ERBB2 amplification occurs in a subset of urothelial carcinomas, but its role as a treatment-selection marker for trastuzumab deruxtecan (T-DXd) remains uncertain. Methods: We retrospectively reviewed four patients with metastatic urothelial carcinoma treated with T-DXd in routine practice from 2024. Treatment selection was based on NGS-detected ERBB2 amplification because HER2 immunohistochemistry and in situ hybridization were unavailable. Results: Four men aged 65–76 years received T-DXd: one in the second line and three in the fourth or fifth line. The best radiological responses, abstracted from contemporaneous radiology reports and oncology medical records, were complete response in one patient, partial response in one, and stable disease in two. Three patients had previously received enfortumab vedotin. Documented adverse events included fatigue, anemia, diarrhea, rash, and leukopenia. No interstitial lung disease or pneumonitis was documented in the available records. Conclusions: These observations are descriptive and hypothesis-generating. They do not establish the efficacy or safety of T-DXd or validate ERBB2 amplification as a predictive biomarker, but they support prospective evaluation of genomic ERBB2 amplification when standard HER2 testing is unavailable. Full article

Human epidermal growth factor receptor 2 (HER2) and trophoblast cell surface antigen 2 (Trop-2) are tumor-associated antigens widely overexpressed in multiple malignant tumors, which drive malignant proliferation, invasion, metastasis, and therapeutic resistance by activating key downstream signaling pathways. Antibody–drug conjugates (ADCs) targeting HER2 and Trop-2 leverage their antigen-specific binding capacity to achieve precise targeted delivery of cytotoxic drugs, representing a significant breakthrough in solid tumor therapy. This review systematically outlines the biological functions and carcinogenic mechanisms of HER2 and Trop-2, focusing on the latest research and development progress of related ADCs. We also summarize and analyze key clinical data and application prospects in breast cancer (BC), gastric cancer (GC), non-small cell lung cancer (NSCLC), and urothelial carcinoma (UC), while also delving into the challenges and future directions within this field. Full article