The role of PIGF blockade in the treatment of colorectal cancer: overcoming the pitfalls

Teresa Macarulla, Clara Montagut, Francisco Javier Sánchez-Martin, Mónica Granja, Helena Verdaguer, Javier Sastre, Josep Tabernero

Research output: Contribution to journalReview articleResearchpeer-review

3 Citations (Scopus)


© 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group. Introduction: In colorectal cancer, anti-VEGF agents have demonstrated a survival benefit when combined with chemotherapy. However, development of resistance is very common. One of the mechanisms is due not to a failure in the VEGFR blockade, but rather to development of compensatory mechanisms of resistance, such as hypoxia-triggered upregulation of other proangiogenic factors, like placental growth factor (PlGF). Areas covered: This article summarizes the fundamental role of PlGF in the development of resistance to antiangiogenic treatment as well as the efficacy of aflibercept, ramucirumab, and regorafenib. Expert opinion: Aflibercept functions as a soluble decoy receptor precluding VEGFs and PlGF from binding to native VEGFR, and therefore preventing the emergence of resistance. Bevacizumab limits its function to preventing the interaction between VEGF-A and VEGFR. In combination with FOLFIRI (VELOUR trial), aflibercept improves survival in patients with metastatic CRC who are resistant or have progressed to oxaliplatin-based chemotherapy. Ramucirumab, a fully humanized immunoglobulin G1 (IgG-1) monoclonal antibody and regorafenib, a multikinase inhibitor, have significant improvement for overall survival as well as for progression-free survival in chemotherapy refractory settings.
Original languageEnglish
JournalExpert Opinion on Biological Therapy
Publication statusPublished - 1 Jan 2019


  • angiogenesis
  • Colorectal cancer
  • placental growth factor
  • resistance to antiangiogenic treatment

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