Precision Warfare in Solid Tumors: Molecular Mechanisms and Emerging Frontiers of Antibody-Drug Conjugates.

Advances in antibody-drug conjugates in cancer: latest updates from the 2026 AACR annual meeting

Highlights from the 2026 American Association for Cancer Research Annual Meeting demonstrate significant advances in ADC design, including dual- and multi-payload constructs, multispecific targeting strategies, and immunostimulatory payloads, with the potential to improve clinical outcomes across diverse cancer types.

Beyond ADCs: Antibody-encapsulated drug for targeted cancer therapy

Antibody-drug conjugates (ADCs) have transformed cancer treatment by covalently linking the monoclonal antibody with cytotoxic payload, yet their clinical potential remains constrained by intrinsic limitations: heterogeneous drug-to-antibody ratios, linker instability, manufacturing complexity, and drug resistance. These challenges highlight the need for fundamentally different drug formulation and delivery platforms. Antibody-encapsulated drugs (AEDs) leverage the single protein encapsulation technology to enable one antibody to noncovalently encapsulate a predefined number of payload molecules. AEDs allow for a fixed drug-to-antibody ratio, mitigate premature drug release, simplify manufacturing, and expand the range of compatible payloads and protein molecules. Preclinical investigation of trastuzumab-encapsulated actinomycin D, a HER2-targeted AED, has demonstrated potent antitumor activity across cancer models with varying HER2 expression levels, alongside a favorable toxicity profile in animal models. The broader translational feasibility of the single protein encapsulation platform is further supported by ongoing clinical trials of albumin-encapsulated therapeutics. Together, these advances position AED as a promising next-generation targeted cancer therapy that complements and potentially extends beyond conventional ADCs, offering a compelling strategy to overcome existing resistance mechanisms and therapeutic limitations.

Antibody–Drug Conjugates in Lung Cancer: Promise, Progress, and Persistent Challenges

The rationale for targeting established and emerging antigens in non-small cell and small cell lung cancer, including HER2, TROP2, c-MET, HER3, CEACAM5, DLL3, and other promising targets currently under clinical investigation are discussed.

Bispecific Antibody-Drug Conjugates in Oncology: Design Principles, Clinical Progress, and Challenges

Linker Design in Antibody-Drug Conjugates: Balancing Stability and Drug Release

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.

Peptide Therapeutics for Solid Tumors: Functional Classes, AI‐Enhanced Discovery and Clinical Advances

This review systematically summarizes advancements in peptide‐based therapeutics for solid tumors from 2020 to 2025, and highlights the transformative role of artificial intelligence (AI) in peptide design and discovery.