Prodrugs for targeted cancer therapy

Author(s)

Souza, Carla ^[1] ; Pellosi, Diogo Silva ^[2] ; Tedesco, Antonio Claudio ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Philosophy Sci & Letters Ribeirao Preto, Dept Chem, Ctr Nanotechnol & Tissue Engn, Ribeirao Preto - Brazil

^[2] Univ Fed Sao Paulo, UNIFESP, Lab Hybrid Mat, Dept Chem, Diadema - Brazil

• Document type: Review article
• Source: EXPERT REVIEW OF ANTICANCER THERAPY; v. 19, n. 6, p. 483-502, JUN 3 2019.
• Web of Science Citations: 1

Abstract

Introduction: Prodrugs have been used to improve the selectivity and efficacy of cancer therapy by targeting unique abnormal markers that are overexpressed by cancer cells and are absent in normal tissues. In this context, different strategies have been exploited and new ones are being developed each year.Areas covered: In this review, an integrated view of the potential use of prodrugs in targeted cancer therapy is provided. Passive and active strategies are discussed in light of the advantages of each one and some successful examples are provided, as well as the clinical status of several prodrugs. Among them, antibody-drug conjugates (ADCs) are the most commonly used. However, several drawbacks, including limited prodrug uptake, poor pharmacokinetics, immunogenicity problems, difficulties in selective targeting and gene expression, and optimized bystander effects limit their clinical applications. Expert opinion: Despite the efforts of different companies and research groups, several drawbacks, such as the lack of relevant in vivo models, complexity of the human metabolism, and economic limitations, have hampered the development of new prodrugs for targeted cancer therapy. As a result, we believe that the combination of prodrugs with cancer nanotechnology and other newly developed approaches, such as aptamer-conjugated nanomaterials, are efficient strategies. (AU)

• FAPESP's process: 16/00389-3 - MULTIFUNCTIONAL NANOPARTICLES FOR SITE-ESPECIFIC DELIVERY OF TEMOZOLOMIDE® AND VERTEPORFIN® FOR COMBINATION THERAPY OF BRAIN TUMORS
• Grantee: Diogo Silva Pellosi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 13/50181-1 - Use of drugs containing nanocarriers with photosensitizers and/or other active compounds applied to cell therapy and treatment of central nervous system disorders
• Grantee: Antonio Claudio Tedesco
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/01272-5 - In vitro reconstituted skin models: development, damage assessment and photoprotective efficacy in the UVA and visible spectral ranges
• Grantee: Carla Souza
• Support Opportunities: Scholarships in Brazil - Post-Doctoral