Management of adverse events associated with TROP2-targeted antibody-drug conjugates in cancer patients.

Innovations in HER2-targeted therapy: A comprehensive review of trastuzumab deruxtecan.

Trastuzumab deruxtecan in non-breast solid tumors: Expanding indications, efficacy, and future directions.

Sarcomas are highly heterogenous and rare malignant tumors derived from mesenchymal cells. The current standard treatments for advanced disease have low response rates and are typically associated with considerable toxicity. The aim of this study was to investigate the expression of a potential novel therapeutic target and its clinical correlation in sarcomas, namely urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180/CD280). We evaluated uPARAP expression in various sarcoma subtypes and in normal tissues using 12 tissue microarrays. Expression was assessed on immunohistochemically stained slides and scored according to staining intensity and the percentage of positive tumor cells. Clinical correlations between uPARAP expression and selected parameters (gender and sample origin) were analyzed using generalized estimating equations, and survival outcomes were evaluated with Kaplan-Meier and log-rank tests. Our results demonstrated limited uPARAP expression in normal tissues, while high expression was observed in the majority of analyzed sarcoma subtypes, particularly high (>80% of highly positive cases) in fibrosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, and various bone sarcomas. Based on the correlation analyses between uPARAP expression and selected clinical parameters or survival outcomes, most subtypes did not show a statistically significant association. In conclusion, this study highlights the potential of uPARAP as an innovative target for targeted treatments, such as novel antibody-drug conjugates in sarcoma.

Aptamers-based drug: A new paradigm for precise treatment.

Genetically encoded self-assembling affibody-streptavidin nanoparticles for HER2-positive cancer theranostics.

Development and In vitro antitumor evaluation of a novel anti-p16 antibody fragment-drug conjugate.

Recent advances in systemic treatment for HER2-negative breast cancer with brain metastases.

Invasive lobular carcinoma (ILC) comprises ∼10%-15% of breast cancers and is characterized by loss of the cell-adhesion molecule E-cadherin (encoded by CDH1), discohesive growth, predominant estrogen receptor (ER) positivity, low-to-intermediate proliferation, and atypical metastatic spread to bone and gastrointestinal/peritoneal sites. Diagnostic assessment is often challenging owing to diffuse infiltration, frequently yielding non-measurable disease per response evaluation criteria in solid tumors (RECIST). Molecularly, ILC is enriched for phosphoinositide 3-kinase (PI3K) activation and harbors emerging vulnerabilities-such as ROS1 synthetic lethality in CDH1-deficient tumors and fibroblast growth factor receptor 1 (FGFR1)/bromodomain and extra-terminal (BET) dependencies-now under study. Because metastatic ILC remains underrepresented in trials, systemic therapy often mirrors invasive ductal carcinoma (IDC). This short communication synthesizes current evidence to distinguish shared from plausibly lobular-specific signals; highlights near-term opportunities-including antibody-drug conjugates (ADCs), oral selective ER degraders (SERDs), and selective use of immunotherapy in an immune-enriched subset with higher tumor-infiltrating lymphocytes (TILs) and PD-L1; and outlines trial-design adaptations-such as incorporating 18F-fluoroestradiol PET (FES-PET)-to improve representation and interpretability in metastatic ILC research.

Delivery science: Its increasing importance for the next generation of medicines.

Advances and perspectives in CEA-targeted therapies: From classic biomarker toward actionable therapeutic target.

Although antibody-drug conjugates (ADCs) have made substantial progress as targeted therapies, the range of suitable ADC payloads remains limited. In this study, the highly N-methylated cyclodepsipeptide [MeAla3-MeAla6]-coibamide (CA) was selected as a novel toxin for ADC construction due to its potent toxicity and unique mechanism of action. Using a quaternary ammonium salt approach, two linker-payload variants, MC-VA-PAB-CA and MC-GGFG-PAB-CA, with distinct cathepsin B (CTB)-cleavable linkers, were synthesized and assessed. Among them, MC-GGFG-PAB-CA demonstrated higher enzyme-responsive cleavage efficiency and superior plasma stability and was selected for conjugation with the epidermal growth factor receptor (EGFR) antibody cetuximab (Ctx), resulting in the formation of Ctx-CA. This conjugate exhibited EGFR-dependent antitumor activity, a pronounced "bystander killing effect", and a significant tumor suppression effect in mouse models. Furthermore, the applicability of this conjugation strategy was confirmed through validation with the HER2 antibody. These findings suggest that CA is a promising weapon for next-generation ADCs.

Radiotherapy resistance remains a major barrier to effective treatment of triple-negative breast cancer (TNBC), highlighting the need to identify mechanisms driving resistance. Here, we identified SDC1 as a pivotal mediator of cancer-associated fibroblast (CAF)-induced radioresistance in breast cancer. SDC1 bound the TIM barrel domain of the glycolytic enzyme ENO1, preventing FBXW7-mediated degradation and driving aerobic glycolysis and lactate accumulation. The resulting lactate-rich microenvironment not only promoted tumor stemness but also significantly impaired the cytotoxic functions of both NK cells and CD8⁺ T cells. Pharmacologic inhibition of ENO1 or lactate export restored radiosensitivity. Targeting SDC1⁺ CAFs with the antibody-drug conjugate indatuximab ravtansine (BT062) synergized with radiotherapy in vivo, markedly reducing tumor burden, depleting stem-like tumor cells, and remodeling the immune microenvironment. These findings define a CAF metabolic program that fuels tumor stemness and rewires the immune microenvironment to confer radioresistance, supporting the therapeutic targeting of SDC1⁺ CAFs in TNBC.

Metastatic gastric cancer remains a major global health challenge with poor long-term outcomes. Over the past 5 years, the treatment landscape has rapidly evolved with the integration of biomarker-informed strategies that guide the use of immune checkpoint inhibitors and targeted therapies in molecularly defined subgroups, including microsatellite unstable, PD-L1-expressing, HER2-positive and claudin 18.2-positive disease. Standard first-line treatment continues to rely on fluoropyrimidine-platinum chemotherapy backbones, with biomarker-driven agents selectively layered on for improved efficacy. Despite these advances, most patients continue to have disease progression, and durable responses are uncommon. In addition to identifying and validating new targets such as FGFR2b, ongoing efforts are focusing on novel strategies involving established targets, including HER2 and claudin 18.2, using next-generation treatment modalities such as antibody-drug conjugates, bispecific antibodies and cellular therapies. Complementary platforms including circulating tumour DNA and theranostic agents are also being explored to better guide treatment selection, facilitate non-invasive monitoring and enable early response assessments. In this Review, we summarize the current standard of care for patients with metastatic gastric cancer and also highlight emerging approaches aimed at improving the outcomes in these patients.

This research analyzes the global landscape of clinical trials focusing on therapies targeting the Nectin cell adhesion molecule 4 (Nectin-4) across various malignancies, using data from the Trialtrove database. Analysis of 136 interventional trials reveals a rapidly expanding field dominated by antibody-drug conjugates, particularly in urothelial carcinoma, with significant activity in combination regimens and diverse therapeutic modalities under exploration. These findings emphasize the substantial translational potential of Nectin-4 and highlight key trends shaping its future clinical development.

The rationale for targeting nectin-4 in pancreatic cancer.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell malignancy and is the most common subtype of lymphoma. Treatment is administered with curative intent and approximately two thirds of patients are expected to have durable long-term survival. To achieve this, anthracycline-based chemotherapy in combination with rituximab is typically administered as initial therapy. Management is optimized based on the disease stage, prognostic clinical features, and histological or molecular subclassification. In patients with the activated B-cell subtype of DLBCL, polatuzumab vedotin is commonly included in the combination. For those with Myc and BCL-2 rearrangements, a more treatment intense approach is used. Despite this risk-adapted approach, at least one third of patients relapse. Those who relapse within 1 year, or are resistant to initial therapy typically receive chimeric antigen receptor (CAR) T-cell therapy. For those relapsing more than a year post initial treatment, salvage chemotherapy followed by an autologous stem cell transplant is offered. In patients ineligible for cellular therapy, or those who progress after CAR T-cell treatment, management is palliative and includes administration of bispecific antibodies or antibody drug conjugate combinations. To further improve the outcome of DLBCL patients, incorporation of cellular and bispecific therapies into front-line treatment is currently being tested.

Antibody-drug conjugates (ADCs) represent a cutting-edge approach in cancer therapy, with monomethyl auristatin E (MMAE) frequently used as a payload in ADC development. We have established a novel bioanalytical method characterized by high sensitivity, accuracy, and efficiency for quantifying MMAE in cynomolgus monkey plasma. MMAE was extracted using liquid-liquid extraction (LLE) and quantified by Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS). Results: The method exhibited excellent linearity across a concentration range of 5 to 3000 pg/mL (r ≥ 0.99) in cynomolgus monkey plasma, it fulfilled precision (CV ≤ 15%, 20% for lower limit of quantification (LLOQ)) and accuracy (83.98-112.75%) criteria according to meeting validation requirements per regulatory bioanalytical validation guidelines. This validated method is instrumental in exploring the in vivo pharmacokinetic profile of ADC and elucidating their exposure-response dynamics.

Non-oncogene-addicted non-small cell lung cancer therapy has seen major advances in recent years. New molecular targets and biomarkers have enabled the development of drugs as diverse as immunotherapies and antibody-drug conjugates, among others. With a pharmacological armamentarium so precise, phase I trials have also evolved from exclusively toxicological studies into early efficacy signal-seeking trials. Nonetheless, difficulties remain, with the frequent failure of new drugs when progressing to a phase III setting. Challenges are seen in the setting of later lines therapy (testing against docetaxel), of which there are several examples. These are being tackled with promising new drugs being developed, based on innovative biological rationales. We review the current state of the art of drug development in non-oncogene-addicted non-small cell lung cancer, including advances, new drugs and targets, challenges, and opportunities in drug development.

Antibody-drug conjugates: from efficacy testing to bioassay evaluation in modern drug development.