Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies

Letizia Procaccio, Vera Damuzzo, Francesca Di Sarra, Alberto Russi, Federica Todino, Vincenzo Dadduzio, Francesca Bergamo, Alessandra Anna Prete, Sara Lonardi, Hans Prenen, Angelo Claudio Palozzo, Fotios Loupakis

Research output: Contribution to journalReview article

Abstract

Angiogenesis is an essential process for tumor growth and metastasis. Inhibition of angiogenesis as an anticancer strategy has shown significant results in a plethora of tumors. Anti-angiogenic agents are currently part of many standard-of-care options for several metastatic gastrointestinal cancers. Bevacizumab, aflibercept, ramucirumab, and regorafenib have significantly improved both progression-free and overall survival in different lines of treatment in metastatic colorectal cancer. Second-line ramucirumab and third-line apatinib are effective anti-angiogenic treatments for patients with metastatic gastric cancer. Unfortunately, the anti-angiogenic strategy has major practical limitations: resistance inevitably develops through redundancy of signaling pathways and selection for subclonal populations adapted for hypoxic conditions. Anti-angiogenic agents may be more effective in combination therapies, with not only cytotoxics but also other emerging compounds in the anti-angiogenic class or in the separate class of the so-called vascular-disrupting agents. This review aims to provide an overview of the approved and "under development" anti-angiogenic compounds as well as the vascular-disrupting agents in the treatment of gastrointestinal cancers, focusing on the actual body of knowledge available on therapy challenges, pharmacodynamic and pharmacokinetic mechanisms, safety profiles, promising predictive biomarkers, and future perspectives.

Original languageEnglish
Pages (from-to)159-179
Number of pages21
JournalDrug Safety
Volume42
Issue number2
DOIs
Publication statusPublished - Feb 2019

Keywords

  • Angiogenesis Inhibitors/administration & dosage
  • Animals
  • Antineoplastic Agents/administration & dosage
  • Drug Development/methods
  • Gastrointestinal Neoplasms/drug therapy
  • Humans
  • Neovascularization, Pathologic/drug therapy
  • Protein Binding/physiology
  • Protein Kinase Inhibitors/administration & dosage
  • Vascular Endothelial Growth Factor A/metabolism

Fingerprint Dive into the research topics of 'Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies'. Together they form a unique fingerprint.

  • Cite this