Targeted therapies articles within Nature Reviews Clinical Oncology

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  • 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

  • Perspectives |

    The goal of personalized therapy is to target tumours with the right drug for the right person at the right time. This is not an easy task, and in this Perspectives article, Funda Meric-Bernstam and Gordon B. Mills tell us about the challenges that need to be overcome and how we should temper the current excitement about targeted therapies with realistic expectations.

    • Funda Meric-Bernstam
    •  & Gordon B. Mills

  • Review Article |

    The identification ofBRCA1 and BRCA2 mutations has affected multiple aspects of breast cancer care, including screening and prevention. The authors discuss therapies that have quickly entered clinical practice and highlight some of the challenges in the development of targeted therapies in BRCA1 and BRCA2mutation carriers, as well as specific issues in the area of diagnostic testing related to these targeted therapies.

    • Kara N. Maxwell
    •  & Susan M. Domchek

  • Perspectives |

    The use of tumour molecular profiles for therapeutic decision making requires that molecular diagnostics be introduced into routine clinical practice. To this end, the French National Cancer Institute and French Ministry of Health have set up a national network of 28 regional molecular genetics centres. In this Perspectives article, the authors look at the 4-year history of the French initiative and discuss its success in rapidly implementing molecular tests for new tumour biomarkers.

    • Frédérique Nowak
    • , Jean-Charles Soria
    •  & Fabien Calvo

  • News & Views |

    The PALETTE randomized phase III trial has reported a statistically significant benefit for the use of pazopanib compared to placebo in terms of progression-free survival for the treatment of soft-tissue sarcoma. However, no benefit in terms of overall survival was observed, the reasons for which might lie in the study design.

    • Isabelle Ray-Coquard
    •  & David Thomas

  • Review Article |

    Neuroblastoma is a debilitating disease and a leading cause of childhood cancer deaths. The discovery of ALK as a mutated oncogenic receptor in neuroblastoma has provided an attractive target for innovative therapies. In this article, Mosse and Carpenter review the preclinical and clinical advances in ALK-targeted therapies for neuroblastoma and discuss the emerging challenges.

    • Erica L. Carpenter
    •  & Yael P. Mossé

  • Review Article |

    Targeting the MET pathway is an increasingly attractive anticancer strategy. In this Review, this pathway is viewed from the clinical perspective, assessing the available agents in terms of efficacy and toxicity and looking forward to biomarker-driven application in the clinic.

    • Solange Peters
    •  & Alex A. Adjei

  • News & Views |

    A qualitative study indicates that there is a positive selection bias towards favourable economic analysis of targeted therapies, when these are funded by the manufacturer. At a time of increasing budgetary constraints and public scrutiny of the relationship between industry and the professions, we need a more mixed economy of funding for this field.

    • David Kerr
    •  & Ahmed Elzawawy

  • 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 |

    In this Review, Tentler et al. present the opportunities and challenges of using patient-derived tumour xenograft models in oncology drug development, provide specific disease examples, and describe concepts regarding predictive biomarker development and future applications.

    • John J. Tentler
    • , Aik Choon Tan
    •  & S. Gail Eckhardt

  • Review Article |

    The advances in the field of targeted therapy for the treatment of renal cell carcinoma have improved outcomes for patients dramatically. In this Review article, an expert consensus opinion for the optimal use of these targeted anticancer therapies for the treatment of patients with renal cell carcinoma is outlined.

    • Bernard Escudier
    • , Cezary Szczylik
    •  & Martin Gore

  • Perspectives |

    This Perspectives article describes how phase I trials assessing the efficacy of targeted therapies should examine not only safety and toxicity, but also the appropriate patient population. Based on the experience of their own academic institution, Rodón and colleagues explain how to build a pre-screening programme in early drug development.

    • Jordi Rodón
    • , Cristina Saura
    •  & Josep Tabernero

  • Review Article |

    Crizotinib has provided dramatic and prolonged benefit for patients with the ALK-positive subtype of non-small-cell lung cancer. Despite these early successes, many challenges remain including understanding the mechanisms of resistance to crizotinib. This Review examines what we already know and the major emerging questions associated with optimal management of this disease.

    • D. Ross Camidge
    •  & Robert C. Doebele

  • News & Views |

    Recent neoadjuvant studies have examined the effects of adding single or dual agents targeting HER2 to chemotherapy, finding unanimously that dual HER2 targeting markedly improves pathologic response. These findings have significant implications for future trial designs, particularly if the impact on pathologic response is accompanied by improved disease-free survival or overall survival.

    • Lisa A. Carey

  • Review Article |

    Despite advances in treating multiple myeloma with the proteasome inhibitor bortezomib and the immunomodulatory drugs thalidomide and lenalidomide, most patients eventually relapse. In this Review, the authors discuss how next-generation inhibitors and immunotherapy agents have been developed based on an improved understanding of the biology of the disease, and highlight the challenges associated with these therapeutic approaches.

    • Anuj Mahindra
    • , Jacob Laubach
    •  & Kenneth Anderson

  • News & Views |

    The BOLERO-2 and CLEOPATRA trials evaluated everolimus for estrogen receptor-positive and pertuzumab for HER2-positive metastatic breast cancer. Both agents enhanced the efficacy of standard therapy, were relatively well tolerated and should be approved for therapeutic use. These data confirm that targeting both major driver and escape pathways improves treatment outcomes.

    • Mothaffar F. Rimawi
    •  & C. Kent Osborne

  • Review Article |

    DNA repair as a therapeutic target has received considerable attention in the treatment of non-small-cell lung cancer (NSCLC). In this Review, Postel-Vinay et al. discuss how optimizing treatment of NSCLC according to DNA-repair biomarkers, such as ERCC1, BRCA1 or RRM1, may aid clinical decision making and improve the outcome of patients with NSCLC.

    • Sophie Postel-Vinay
    • , Elsa Vanhecke
    •  & Jean-Charles Soria

  • Opinion |

    Antiangiogenic therapies have secured a role in the treatment of multiple cancers. However, the success of this targeted therapy is not as great as originally anticipated. In this Perspectives article, the authors use data from clinical trials to uncover where some of the problems with this therapy lie, discuss exciting recently published data and look to what the next steps should be.

    • Gordon C. Jayson
    • , Daniel J. Hicklin
    •  & Lee M. Ellis

  • Year in Review |

    Options to treat late-stage castration-resistant prostate cancer continued to increase in 2011, as three agents with different mechanisms of action prolonged life and a fourth reduced the morbidity of skeletal metastases. These outcomes contrasted with the heightened controversy generated by the recommendation against PSA screening and other early detection strategies.

    • Yu Chen
    •  & Howard I. Scher

  • Year in Review |

    2011 saw improvements in our understanding of B-cell malignancies: insights into the genomic basis of chronic lymphocytic leukemia were achieved; reduced treatment intensity caused fewer toxic effects in early-stage Hodgkin lymphoma; first-line rituximab maintenance therapy improved outcome in follicular lymphoma; and selected patients with diffuse large-cell lymphoma benefited from the addition of bortezomib.

    • Paula Cramer
    •  & Michael Hallek

  • Review Article |

    Recent phase III trials of denosumab, a monoclonal antibody that inhibits RANKL, have demonstrated superiority over zoledronic acid in reducing skeletal morbidity in patients with metastatic bone disease. Brown and Coleman describe the emerging role of denosumab in maintaining bone health in the oncology setting and discuss the factors to consider when deciding whether to use bisphosphonates or denosumab in clinical practice.

    • Janet E. Brown
    •  & Robert E. Coleman

  • Year in Review |

    Bone-targeting treatments have transformed the quality of life of patients with metastatic bone disease. 2011 saw the emergence of denosumab—a RANK ligand-specific antibody—as a more-effective alternative treatment to bisphosphonates and of data on the use of bone-targeting treatments to prevent metastasis from breast and prostate cancers.

    • Robert E. Coleman

  • Review Article |

    This Review article approaches the area of targeted therapies from two angles: efficacy and side effects. The authors outline the successes that have been achieved in treating cancer with targeted therapies and also discuss the pitfalls and quality of life issues that still need to be addressed.

    • Dorothy M. K. Keefe
    •  & Emma H. Bateman

  • Review Article |

    If a targeted therapy demonstrates convincing efficacy in early clinical testing, can randomized phase III trials be avoided? Sharma and Schilsky discuss when it is reasonable to consider foregoing randomized phase III trials before drug approval and also highlight the caveats. They explore the consequences of such an approach and propose criteria that the drugs must meet to be approved without a phase III trial.

    • Manish R. Sharma
    •  & Richard L. Schilsky

  • Review Article |

    Despite the advent of HER2-directed therapies, many patients with HER2-positive early stage breast cancer relapse and die of this disease. Trials to define, refine and optimize the use of the approved HER2-targeted agents are ongoing. New approaches are being developed and a series of large trials in the adjuvant and neoadjuvant settings are planned or in progress. In this Review, Arteaga et al. describe the current treatment for HER2-positive breast cancer and provide an update on ongoing clinical trials and translational research.

    • Carlos L. Arteaga
    • , Mark X. Sliwkowski
    •  & Luca Gianni

  • Review Article |

    This Review discusses recent evidence that indicates that different genetic alterations might be related to distinct sensitivity to targeted therapies. It examines prototypical examples and asks what is the role of cancer mutations as predictors of sensitivity and resistance to targeted therapies? Further, what are the implications for the 'personalized' treatment of cancer patients?

    • Miriam Martini
    • , Loredana Vecchione
    •  & Alberto Bardelli

  • News & Views |

    The AZURE trial data add to the uncertainty of whether adjuvant bisphophonates are a valuable addition to the armamentarium in the treatment of early stage breast cancer. Although the overall trial results were negative, a prespecified subgroup analysis demonstrated a 25% reduction in the risk of relapse and death in postmenopausal patients.

    • Michael Gnant

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