Tumour angiogenesis articles within Nature Reviews Clinical Oncology

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  • Perspective |

    The benefit of combining antiangiogenic agents with immune-checkpoint inhibitors has been demonstrated in pivotal phase III trials across different cancer types, some with practice-changing results; however, other phase III trials have had negative results. The authors of this Perspective discuss the variable outcomes of these trials, considering factors that account for these differences and suggesting future initiatives for improving the outcomes in patients receiving these combinations.

    • Hung-Yang Kuo
    • , Kabir A. Khan
    •  & Robert S. Kerbel

  • Perspective |

    Anti-angiogenic therapy has the capacity to ameliorate antitumour immunity and, thus, some combinations of anti-angiogenics and immunotherapies have been approved and a number of them are being tested. The authors of this Perspective describe how the angiogenesis-induced endothelial immune cell barrier hampers antitumour immunity and the role of endothelial cell anergy as a vascular counterpart of immune checkpoints.

    • Zowi R. Huinen
    • , Elisabeth J. M. Huijbers
    •  & Arjan W. Griffioen

  • Perspective |

    An immunosuppressive tumour microenvironment is one of the main reasons why patients with solid tumours fail to respond to immune-checkpoint inhibition. In this Perspective, the authors describe the potential of nanomedicines to normalize the tumour microenvironment, thus overcoming this immunosuppressive barrier and enabling greater numbers of patients to respond to immune-checkpoint inhibition.

    • John D. Martin
    • , Horacio Cabral
    •  & Rakesh K. Jain

  • Review Article |

    Despite much hope, anti-angiogenic agents have largely failed to achieve the promise demonstrated in preclinical models. In this Review, the authors discuss an alternative hypothesis — vessel co-option — that might explain many of these failures and describe the evidence for a role of this largely overlooked aspect of tumour biology.

    • Elizabeth A. Kuczynski
    • , Peter B. Vermeulen
    •  & Andrew R. Reynolds

  • Opinion |

    The aberrant tumour vasculature and the associated angiogenic factors have been implicated in tumour immune evasion and progression. Herein, the authors provide their perspectives on how normalization of the tumour microenvironment using antiangiogenic agents could potentially increase the effectiveness of immunotherapies and improve the outcomes of patients with cancer. The authors also highlight important considerations for future research in this area.

    • Dai Fukumura
    • , Jonas Kloepper
    •  & Rakesh K. Jain

  • Review Article |

    The combination of immunotherapies with other therapeutic modalities, including anti-angiogenic agents, is currently under investigation to improve the outcomes of patients receiving immunotherapies. In this article, the authors review the effects mediated by anti-angiogenic agents that might increase the efficacy of immunotherapies and discuss the possibility that immunotherapies might increase the efficacy of anti-angiogenic agents and/or promote changes in the tumour vasculature.

    • Kabir A. Khan
    •  & Robert S. Kerbel

  • Review Article |

    Both multiple myeloma and acute myeloid leukaemia are often preceded by defined precursor stages of neoplasia, which can aid efforts to unravel the mechanisms of disease progression. Herein, the authors review studies of the important roles of microenvironmental factors in promoting the development and progression of haematological cancers in these precursor conditions. Potential therapeutic strategies targeting the abnormal bone-marrow microenvironment are discussed.

    • Irene M. Ghobrial
    • , Alexandre Detappe
    •  & David P. Steensma

  • Year in Review |

    2017 saw the publication of clinical trial data and the approval of new treatment approaches for metastatic urothelial carcinoma. Pembrolizumab is now a well-established treatment for patients with disease progression after cisplatin, with high-level evidence supporting its superiority over second-line chemotherapy. For patients ineligible for cisplatin, atezolizumab and pembrolizumab provide meaningful clinical benefit as frontline therapies.

    • Joaquim Bellmunt
    •  & Rosa Nadal

  • Review Article |

    Metronomic chemotherapy regimens were developed to optimize the antitumour efficacy of antiangiogenic agents and to reduce toxicity of antineoplastic drugs, but the effectiveness of this approach also relies on other mechanisms, such as the stimulation of the immune system. Investigating the pharmacokinetic and pharmacodynamic properties of agents administered in metronomic regimens will enable a more-personalized therapeutic approach. Herein, Bocci and Kerbel discuss results from early phase and pilot clinical studies that support the important link between pharmacokinetics and metronomic chemotherapy.

    • Guido Bocci
    •  & Robert S. Kerbel

  • News & Views |

    The RAINBOW study has demonstrated that ramucirumab plus paclitaxel as second-line treatment for advanced-stage gastric cancer prolongs survival compared with paclitaxel alone. These data confirm that ramucirumab represents a new effective treatment option for gastric cancer. Nevertheless, new treatment options remain eagerly awaited in this disease with dismal outcomes.

    • Florian Lordick

  • Review Article |

    Metronomic chemotherapy has undergone major advances as an antiangiogenic therapy. The discovery of the pro-immune properties of chemotherapy has established the intrinsic multitargeted nature of this therapeutic approach. André et al. describe the complex mechanisms of action of metronomic chemotherapy, and discuss the latest clinical data in both adult and paediatric populations, highlighting its potential role in the era of personalized medicine.

    • Nicolas André
    • , Manon Carré
    •  & Eddy Pasquier

  • Review Article |

    The association between cancer and angiogenesis has been established for decades, but it is only in the past 10 years that the concept of cancer prevention using antiangiogenic agents has emerged. This Review outlines the mechanisms of action of these preventative agents and proposes that there should be four levels of angioprevention, depending on the cancer risk.

    • Adriana Albini
    • , Francesca Tosetti
    •  & William W. Li

  • Review Article |

    Cancer cells rely on angiogenesis to fulfil their need for oxygen and nutrients; hence, agents targeting angiogenic pathways and mediators have been investigated as potential cancer drugs. However, a significant number of patients either do not respond to antiangiogenic agents or fairly rapidly develop resistance to them, which raises questions about how resistance develops and how it can be overcome. In this Review, the authors examine the evidence linking antiangiogenic agents and intratumour hypoxia by providing an overview of the preclinical and clinical data, focusing on the possibility of exploiting intratumour hypoxia as a means to improve the therapeutic response to antiangiogenic agents.

    • Annamaria Rapisarda
    •  & Giovanni Melillo

  • Review Article |

    Hepatocellular carcinoma (HCC) is notoriously resistant to systemic therapies. The success of the anti-VEGF therapy sorafenib in patients with advanced-stage HCC raises hope as well as critical questions on the future development of targeted agents including other antiangiogenic drugs.

    • Andrew X. Zhu
    • , Dan G. Duda
    •  & Rakesh K. Jain

  • Review Article |

    The progression-free survival benefits from approved antiangiogenic drugs are modest and are frequently not accompanied by overall survival improvements. Recent disappointing clinical trial results (for example AVANT) have highlighted questions about the basis of drug resistance, the limitations of predictive preclinical models, and whether antiangiogenic therapy may lead to more invasive or metastatic tumor behavior.

    • John M. L. Ebos
    •  & Robert S. Kerbel

  • Opinion |

    Antiangiogenic therapy inhibits tumor growth by targeting the blood vessels of the tumor. Antiangiogenic therapy often correlates with longer survival in patients without affecting tumor growth. This positive response may be due to the off-tumor target effects of antiangiogenic drugs. In this article, Yihai Cao describes the potential mechanisms underlying the benefits of targeting off-tumor sites, and how these events improve outcomes in patients with cancer-associated systemic syndromes.

    • Yihai Cao

  • Review Article |

    Metronomic chemotherapy is the chronic administration of chemotherapeutic agents at relatively low, minimally toxic doses, and with no prolonged drug-free breaks. This type of chemotherapy inhibits tumor growth primarily through anti-angiogenic mechanisms. The latest clinical trials of metronomic chemotherapy in adult and pediatric cancer patients are discussed and the authors highlight the research efforts that need to be made to facilitate the optimal development of metronomic chemotherapy in the clinic.

    • Eddy Pasquier
    • , Maria Kavallaris
    •  & Nicolas André

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