Drug development articles within Nature Reviews Clinical Oncology

Featured

  • Review Article |

    Active immunotherapy is emerging as an important addition to conventional cancer treatments, but many important questions remain. Optimal combinations of antigens, adjuvants and delivery vehicles need to be determined and effective strategies for overcoming tumour-associated immunosuppression ought to be developed. This Review provides an overview of new results from clinical studies of therapeutic cancer vaccines directed against tumour-associated antigens and discusses their implications for the use of active immunotherapy.

    • Ignacio Melero
    • , Gustav Gaudernack
    •  & Håkan Mellstedt

  • Opinion |

    The current drug development procedures are far from optimal, owing to the continuous development of the health systems and the clinical research landscape. The European Organisation for Research and Treatment of Cancer proposes in this Perspective the use of collaborative molecular screening platforms (CMSPs) as a new approach for drug development. These CMSPs have the advantage of optimizing expertise of several partners and combining efforts alongside with cost-sharing models for efficient patient selection.

    • Denis Lacombe
    • , Sabine Tejpar
    •  & Roger Stupp

  • Review Article |

    MEK1 and MEK2 have key roles in tumorigenesis and, therefore, represent promising targets for cancer therapy; however, MEK1/2 inhibitors have been shown to have efficacy in only a narrow range of cancer types, mainly tumours that harbourBRAF or NRASmutations. In this article, the clinical experience with MEK inhibitors to date is reviewed, and potential approaches to overcoming therapeutic resistance and increasing the efficacy of treatment are discussed.

    • Yujie Zhao
    •  & Alex A. Adjei

  • Review Article |

    Over 70 years ago, Huggins and Hodges discovered that prostate cancer depends on androgens. Since then, targeting the androgen receptor signaling pathway has remained the backbone of prostate cancer treatment. This Review discusses the past, present and future of androgen receptor targeting therapeutics.

    • Yien Ning Sophia Wong
    • , Roberta Ferraldeschi
    •  & Johann de Bono

  • Review Article |

    Metastatic prostate cancer and its treatment are associated with skeletal complications, which cause some of the most distressing symptoms as well as being associated with poor survival. This Review addresses the therapeutic options that exist to treat the morbidity associated with skeletal-related events.

    • Benjamin A. Gartrell
    •  & Fred Saad

  • Review Article |

    Chemotherapeutic agents targeting thymidylate biosynthesis, and particularly the enzyme thymidylate synthase, have now been key cancer therapies for 60 years. In this article, the classic and novel approaches to targeting this metabolic pathway and strategies for overcoming drug resistance mechanisms are comprehensively reviewed.

    • Peter M. Wilson
    • , Peter V. Danenberg
    •  & Robert D. Ladner

  • Review Article |

    Identification of the optimal dose remains a key challenge in drug development. The standard approach that is based on identifying the maximum tolerated dose does not take into account important aspects of clinical pharmacology for newer targeted agents. The authors discuss adaptations to dose-finding trials for molecularly-targeted agents that enable more-efficient trials in the future in terms of costs and, most importantly, optimal patient benefit.

    • Ron H. J. Mathijssen
    • , Alex Sparreboom
    •  & Jaap Verweij

  • Review Article |

    Luminal breast cancer is the most-frequently occurring subtype of breast cancer, but it is a highly heterogeneous disease. Data are emerging to assist in the stratification of patients to the optimal treatment and to address therapy resistance. This Review outlines the biology of this disease, and discusses the treatment options and ongoing studies for women with oestrogen receptor-positive breast cancer.

    • Michail Ignatiadis
    •  & Christos Sotiriou

  • 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 current system for the development of anticancer drugs is not fit for purpose. In this Review article, this system is examined from the perspective of the drug company, offering a fresh look at development from target identification up to registration.

    • Eric H. Rubin
    •  & D. Gary Gilliland

  • Opinion |

    In terms of drug development, the main driving force should be optimized benefit–risk to patients; however, no drug can be of real benefit unless it has achieved approval from the regulatory agencies. This Perspectives allows us a peek behind the door of one of those agencies (EMA) and outlines the hurdles that exist and that need to be overcome before we can have an efficient, biomarker-driven drug development program. Points for discussion in the community are raised and suggestions are put forward.

    • Bertil Jonsson
    •  & Jonas Bergh

  • Year in Review |

    Melanoma has emerged as the paradigm tumor for drug development through mutation-targeted therapies (inhibitors targeting BRAF, MEK, and c-KIT) and immunotherapy. Exploring the combinations of both approaches is a challenge that will require scientific rationale and the cooperation of the pharmaceutical industry. But, with these challenges comes another opportunity to change the paradigms in drug development.

    • Alexander M. M. Eggermont
    •  & Caroline Robert

  • 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 |

    Small-cell lung cancer has a poor prognosis and treatment options for this disease are limited. The authors discuss the molecular biology and current clinical management of progressive small-cell lung cancer, and critically evaluate the recent SPEAR trial, in which the use of second-line picoplatin was investigated.

    • William N. William Jr
    •  & Bonnie S. Glisson

  • News & Views |

    In the NOAH clinical trial, trastuzumab treatment for locally advanced breast cancer was associated with increased complete and overall response rate and improved event-free survival. The ability to identify this advantage in a relatively smaller number of patients (compared with adjuvant therapy trials) suggests that the neoadjuvant setting might serve to inform the design of adjuvant trials and indicate appropriate off-study adjuvant therapy.

    • Heather L. McArthur
    •  & Clifford A. Hudis

  • Review Article |

    Mammalian target of rapamycin (mTOR) has a key role in several pathways that are involved in cell growth and cancer. In this Review, Dr. Dancey outlines the mechanisms of action and performance of current mTOR inhibitors in clinical trials. Second-generation inhibitors are also discussed along with strategies that should be used to improve outcomes achieved with mTOR inhibitors.

    • Janet Dancey

  • News & Views |

    In Japan, it is quite rare for an investigator to submit an investigational new drug application to initiate a clinical trial and obtain approval of a drug on the basis of clinical trial results. This means that development of new therapies is currently driven almost entirely by pharmaceutical companies as opposed to independent investigators. Here, we provide our perspective on the reasons for this situation and advocate investigator-initiated cancer drug development as a means of increasing access to better therapies for Japanese cancer patients.

    • Chiyo K. Imamura
    • , Naoko Takebe
    •  & Naoto T. Ueno

Browse broader subjects

Browse Drug development across other nature.com journals