Relationship between hypoxia and response to antiangiogenic therapy in metastatic colorectal cancer

Research output: Contribution to journalReview article

Abstract

Colorectal cancer remains a major public health problem worldwide. Despite the introduction of antiangiogenic drugs for the treatment of metastatic disease, a large number of issues remains unresolved. In particular, studies on predictive biomarkers of response and pathways of resistance to these agents are lacking, making it difficult to accurately select candidates for treatment. Hypoxia is the prime driving force for tumor angiogenesis and a vicious cycle between hypoxia and angiogenesis can be observed in tumors. Anti-angiogenic drugs act inhibiting tumor vasculature and, as consequence, inducing hypoxia. However, hypoxia could, in turn, induce an increase of metastatic potential of cells and a series of phenomena that could induce drug resistance. In the present review biological mechanisms of hypoxia and its relation with angiogenesis, and resistance to antiangiogenic therapy will be discussed. Moreover, data from clinical trials on antiangiogenic drugs in metastatic colorectal cancer will be reviewed, and the role of hypoxia in monitoring the response to treatment will be analysed. Combination strategies using anti-angiogenic and hypoxia inhibiting drugs are also discussed as they constitute promising field of research.

Original languageEnglish
Pages (from-to)46678-46691
Number of pages14
JournalOncotarget
Volume7
Issue number29
DOIs
Publication statusPublished - 2016

Fingerprint

Colorectal Neoplasms
Therapeutics
Pharmaceutical Preparations
Neoplasms
Angiogenesis Inhibitors
Hypoxia
Drug Resistance
Public Health
Biomarkers
Clinical Trials
Research

Keywords

  • Angiogenesis
  • Antiangiogenic therapy
  • Bevacizumab
  • Hypoxia
  • Metastatic colorectal cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Relationship between hypoxia and response to antiangiogenic therapy in metastatic colorectal cancer. / Ulivi, Paola; Marisi, Giorgia; Passardi, Alessandro.

In: Oncotarget, Vol. 7, No. 29, 2016, p. 46678-46691.

Research output: Contribution to journalReview article

@article{63069412edd8440796668e5f755c27c9,
title = "Relationship between hypoxia and response to antiangiogenic therapy in metastatic colorectal cancer",
abstract = "Colorectal cancer remains a major public health problem worldwide. Despite the introduction of antiangiogenic drugs for the treatment of metastatic disease, a large number of issues remains unresolved. In particular, studies on predictive biomarkers of response and pathways of resistance to these agents are lacking, making it difficult to accurately select candidates for treatment. Hypoxia is the prime driving force for tumor angiogenesis and a vicious cycle between hypoxia and angiogenesis can be observed in tumors. Anti-angiogenic drugs act inhibiting tumor vasculature and, as consequence, inducing hypoxia. However, hypoxia could, in turn, induce an increase of metastatic potential of cells and a series of phenomena that could induce drug resistance. In the present review biological mechanisms of hypoxia and its relation with angiogenesis, and resistance to antiangiogenic therapy will be discussed. Moreover, data from clinical trials on antiangiogenic drugs in metastatic colorectal cancer will be reviewed, and the role of hypoxia in monitoring the response to treatment will be analysed. Combination strategies using anti-angiogenic and hypoxia inhibiting drugs are also discussed as they constitute promising field of research.",
keywords = "Angiogenesis, Antiangiogenic therapy, Bevacizumab, Hypoxia, Metastatic colorectal cancer",
author = "Paola Ulivi and Giorgia Marisi and Alessandro Passardi",
year = "2016",
doi = "10.18632/oncotarget.8712",
language = "English",
volume = "7",
pages = "46678--46691",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals LLC",
number = "29",

}

TY - JOUR

T1 - Relationship between hypoxia and response to antiangiogenic therapy in metastatic colorectal cancer

AU - Ulivi, Paola

AU - Marisi, Giorgia

AU - Passardi, Alessandro

PY - 2016

Y1 - 2016

N2 - Colorectal cancer remains a major public health problem worldwide. Despite the introduction of antiangiogenic drugs for the treatment of metastatic disease, a large number of issues remains unresolved. In particular, studies on predictive biomarkers of response and pathways of resistance to these agents are lacking, making it difficult to accurately select candidates for treatment. Hypoxia is the prime driving force for tumor angiogenesis and a vicious cycle between hypoxia and angiogenesis can be observed in tumors. Anti-angiogenic drugs act inhibiting tumor vasculature and, as consequence, inducing hypoxia. However, hypoxia could, in turn, induce an increase of metastatic potential of cells and a series of phenomena that could induce drug resistance. In the present review biological mechanisms of hypoxia and its relation with angiogenesis, and resistance to antiangiogenic therapy will be discussed. Moreover, data from clinical trials on antiangiogenic drugs in metastatic colorectal cancer will be reviewed, and the role of hypoxia in monitoring the response to treatment will be analysed. Combination strategies using anti-angiogenic and hypoxia inhibiting drugs are also discussed as they constitute promising field of research.

AB - Colorectal cancer remains a major public health problem worldwide. Despite the introduction of antiangiogenic drugs for the treatment of metastatic disease, a large number of issues remains unresolved. In particular, studies on predictive biomarkers of response and pathways of resistance to these agents are lacking, making it difficult to accurately select candidates for treatment. Hypoxia is the prime driving force for tumor angiogenesis and a vicious cycle between hypoxia and angiogenesis can be observed in tumors. Anti-angiogenic drugs act inhibiting tumor vasculature and, as consequence, inducing hypoxia. However, hypoxia could, in turn, induce an increase of metastatic potential of cells and a series of phenomena that could induce drug resistance. In the present review biological mechanisms of hypoxia and its relation with angiogenesis, and resistance to antiangiogenic therapy will be discussed. Moreover, data from clinical trials on antiangiogenic drugs in metastatic colorectal cancer will be reviewed, and the role of hypoxia in monitoring the response to treatment will be analysed. Combination strategies using anti-angiogenic and hypoxia inhibiting drugs are also discussed as they constitute promising field of research.

KW - Angiogenesis

KW - Antiangiogenic therapy

KW - Bevacizumab

KW - Hypoxia

KW - Metastatic colorectal cancer

UR - http://www.scopus.com/inward/record.url?scp=84979872943&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979872943&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.8712

DO - 10.18632/oncotarget.8712

M3 - Review article

AN - SCOPUS:84979872943

VL - 7

SP - 46678

EP - 46691

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 29

ER -