The role of tumor angiogenesis as a therapeutic target in colorectal cancer

Francesca Battaglin, Alberto Puccini, Rossana Intini, Marta Schirripa, Alessandra Ferro, Francesca Bergamo, Sara Lonardi, Vittorina Zagonel, Heinz-Josef Lenz, Fotios Loupakis

Research output: Contribution to journalReview article

Abstract

INTRODUCTION: Angiogenesis is a complex process regulated by several pro- and anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role in colorectal cancer (CRC) development and progression. Therapeutic agents targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be effective across different treatment lines in metastatic CRC (mCRC) and contributed greatly to improve patients' survival in recent years. Areas covered: This review aimed to summarize the actual body of knowledge available on the VEGF pathway in CRC, including currently available anti-angiogenic drugs and treatment challenges, mechanisms of resistance, promising predictive biomarkers and future perspectives. Expert commentary: Angiogenesis inhibition in subsequent lines of treatment is a valid strategy in the continuum of care of mCRC patients. In this scenario, the availability of multiple agents warrants to tailor therapy to an individualized approach. However, the validation of predictive biomarkers to aid therapeutic decisions remains an issue. Intrinsic and adaptive resistance to anti-angiogenic agents comprises distinct and intertwined processes, eventually leading to treatment failure and disease progression. The expanding knowledge on the mechanisms underlying the angiogenesis pathway, different potential treatment targets and mechanisms of tumor resistance, may lead to promising new perspectives in this field.

Original languageEnglish
Pages (from-to)251-266
Number of pages16
JournalExpert Review of Anticancer Therapy
Volume18
Issue number3
DOIs
Publication statusPublished - Mar 2018

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Colorectal Neoplasms
Neoplasms
Vascular Endothelial Growth Factor A
Therapeutics
Biomarkers
Continuity of Patient Care
Angiogenesis Inhibitors
Decision Support Techniques
Angiogenesis Inducing Agents
Treatment Failure
Disease Progression
Survival

Keywords

  • Angiogenesis Inhibitors/administration & dosage
  • Antineoplastic Agents/administration & dosage
  • Biomarkers, Tumor/metabolism
  • Colorectal Neoplasms/blood supply
  • Disease Progression
  • Drug Resistance, Neoplasm
  • Humans
  • Neovascularization, Pathologic/drug therapy
  • Receptors, Vascular Endothelial Growth Factor/antagonists & inhibitors
  • Survival
  • Vascular Endothelial Growth Factor A/antagonists & inhibitors

Cite this

The role of tumor angiogenesis as a therapeutic target in colorectal cancer. / Battaglin, Francesca; Puccini, Alberto; Intini, Rossana; Schirripa, Marta; Ferro, Alessandra; Bergamo, Francesca; Lonardi, Sara; Zagonel, Vittorina; Lenz, Heinz-Josef; Loupakis, Fotios.

In: Expert Review of Anticancer Therapy, Vol. 18, No. 3, 03.2018, p. 251-266.

Research output: Contribution to journalReview article

Battaglin, Francesca ; Puccini, Alberto ; Intini, Rossana ; Schirripa, Marta ; Ferro, Alessandra ; Bergamo, Francesca ; Lonardi, Sara ; Zagonel, Vittorina ; Lenz, Heinz-Josef ; Loupakis, Fotios. / The role of tumor angiogenesis as a therapeutic target in colorectal cancer. In: Expert Review of Anticancer Therapy. 2018 ; Vol. 18, No. 3. pp. 251-266.
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AU - Battaglin, Francesca

AU - Puccini, Alberto

AU - Intini, Rossana

AU - Schirripa, Marta

AU - Ferro, Alessandra

AU - Bergamo, Francesca

AU - Lonardi, Sara

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N2 - INTRODUCTION: Angiogenesis is a complex process regulated by several pro- and anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role in colorectal cancer (CRC) development and progression. Therapeutic agents targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be effective across different treatment lines in metastatic CRC (mCRC) and contributed greatly to improve patients' survival in recent years. Areas covered: This review aimed to summarize the actual body of knowledge available on the VEGF pathway in CRC, including currently available anti-angiogenic drugs and treatment challenges, mechanisms of resistance, promising predictive biomarkers and future perspectives. Expert commentary: Angiogenesis inhibition in subsequent lines of treatment is a valid strategy in the continuum of care of mCRC patients. In this scenario, the availability of multiple agents warrants to tailor therapy to an individualized approach. However, the validation of predictive biomarkers to aid therapeutic decisions remains an issue. Intrinsic and adaptive resistance to anti-angiogenic agents comprises distinct and intertwined processes, eventually leading to treatment failure and disease progression. The expanding knowledge on the mechanisms underlying the angiogenesis pathway, different potential treatment targets and mechanisms of tumor resistance, may lead to promising new perspectives in this field.

AB - INTRODUCTION: Angiogenesis is a complex process regulated by several pro- and anti-angiogenic factors, thus the loss of its fine equilibrium plays a key role in colorectal cancer (CRC) development and progression. Therapeutic agents targeting VEGF/VEGFR signaling, the main regulator of this process, proved to be effective across different treatment lines in metastatic CRC (mCRC) and contributed greatly to improve patients' survival in recent years. Areas covered: This review aimed to summarize the actual body of knowledge available on the VEGF pathway in CRC, including currently available anti-angiogenic drugs and treatment challenges, mechanisms of resistance, promising predictive biomarkers and future perspectives. Expert commentary: Angiogenesis inhibition in subsequent lines of treatment is a valid strategy in the continuum of care of mCRC patients. In this scenario, the availability of multiple agents warrants to tailor therapy to an individualized approach. However, the validation of predictive biomarkers to aid therapeutic decisions remains an issue. Intrinsic and adaptive resistance to anti-angiogenic agents comprises distinct and intertwined processes, eventually leading to treatment failure and disease progression. The expanding knowledge on the mechanisms underlying the angiogenesis pathway, different potential treatment targets and mechanisms of tumor resistance, may lead to promising new perspectives in this field.

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