Receptor-Mediated Drug Delivery: Redefining Targeted Drug Conjugates in Oncology.

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Targeted drug delivery (TDD) utilizes ligand-drug conjugates for selective cancer cell targeting.
• Exploiting overexpressed cell surface receptors (CSRs) facilitates receptor-mediated endocytosis of drug conjugates.
• Minimizing normal tissue uptake enhances the safety profile of cytotoxic payloads.

Purpose of the Study:

• To review clinically validated and emerging cell surface receptors (CSRs) for targeted drug delivery (TDD) in oncology.
• To discuss the impact of CSR characteristics and drug conjugate design on therapeutic outcomes.
• To guide the development of next-generation TDD platforms for improved cancer treatment.

Main Methods:

• Literature review of FDA-approved drug conjugates and emerging CSR targets.
• Analysis of factors influencing tumor drug accumulation and therapeutic efficacy.
• Elucidation of design principles for potent ligands and drug conjugates.

Main Results:

• Delineation of four clinically validated CSRs (HER2, Trop-2, Nectin-4, SSTR2) with approved conjugates.
• Highlighting emerging CSRs (EGFR, DLL3, keratin 1) for future TDD platforms.
• Discussion on how CSR properties and conjugate design dictate efficacy.

Conclusions:

• Strategic selection and optimization of CSRs and conjugate design are crucial for effective TDD in cancer.
• Refining parameters like ligand affinity, linker stability, and CSR endocytosis mechanisms can enhance drug accumulation.
• This knowledge facilitates the development of more potent TDD agents to improve cytotoxic therapy outcomes.