Drug discovery articles within Nature Reviews Clinical Oncology

Featured

  • Review Article |

    Growing evidence indicates that anticancer agents can mobilize the immune system against the tumour. By reinstating immunosurveillance, the activity of conventional and targeted therapies might be prolonged beyond cessation of the treatment. The authors of this Review, explore how imatinib likely operates through immune and cell-autonomous mechanisms, which has practical implications for defining biomarkers that predict response or resistance to imatinib, as well as for the design of novel combination treatments.

    • Laurence Zitvogel
    • , Sylvie Rusakiewicz
    •  & Guido Kroemer

  • News & Views |

    Accurate and efficient expedited investigational new drug (IND) reporting is a crucial component of clinical research. The FDA, pharmaceutical companies, institutional review boards, and clinical investigators should develop dynamic standardized electronic forms with preferred, predetermined terms to harmonize their practices and to help optimize the quality of clinical research and maximize patient safety.

    • Apostolia M. Tsimberidou

  • Review Article |

    The aim of immunotherapy is to treat cancer by enabling the immune system to attack the tumour. In the past decade, remarkable results have been obtained in clinical trials with immunotherapy for patients with advanced-stage cancer. Two types of immunotherapy have been used in the majority of trials conducted in the past decade: immune cell-targeted antibody therapy and adoptive cellular therapy. Herein, the latest advances in both modalities are discussed, including settings for which testing combination strategies and 'armoured' CAR T cells are recommended.

    • Danny N. Khalil
    • , Eric L. Smith
    •  & Jedd D. Wolchok

  • News & Views |

    A survey on the official prices of 31 cancer drugs across 18 countries, published by Vogler and colleagues, has revealed substantial differences in price for the same drug in different countries. Herein, we discuss inequalities in the access to cancer care and raise some challenging questions.

    • Richard Sullivan
    •  & Ajay Aggarwal

  • Year in Review |

    Advances in key areas of research have enabled improved outcomes for patients diagnosed with ovarian cancer in the past three decades. In 2015, this trend was maintained with important progress in areas such as guideline compliance, design of targeted approaches and molecular profiling.

    • Robert L. Coleman

  • News & Views |

    Henderson and colleagues previously highlighted the need for more-rigorous standards of preclinical experimental design and reporting metrics. They now build on their earlier work with a meta-analysis of preclinical experiments that examined the efficacy of sunitinib. Their results demonstrate how suboptimal preclinical study designs can prompt unwarranted clinical expectations.

    • Eric E. Gardner
    •  & Charles M. Rudin

  • News & Views |

    In the RADIANT study, no difference in disease-free survival was observed for patients with non-small-cell lung cancer (NSCLC) treated with erlotinib versus placebo in the adjuvant setting. Further biomarker studies are awaited to determine whether patients with NSCLC can benefit from adjuvant therapy with tyrosine kinase inhibitors.

    • Fred R. Hirsch
    •  & Paul A. Bunn Jr

  • Review Article |

    Cardiotoxic effects of chemotherapy can occur in various different ways depending upon the type of chemotherapy used and various patient characteristics. In this Review, the authors describe the established cardiotoxic effects of anthracyclines and HER2 inhibitors, and describe a systems medicine approach that might enable the optimal management of acute and chronic cardiotoxcities in patients who are receiving, or have received, these therapies.

    • Sherry-Ann Brown
    • , Nicole Sandhu
    •  & Joerg Herrmann

  • News & Views |

    Dose-expansion cohorts (DECs) enable investigators to identify potentially effective drugs, for specific patient populations, in a single trial by assessing antitumour activity as early as possible. We discuss how the objectives, design and interpretation of DEC have evolved, and how DECs are changing the landscape of early drug development.

    • Alexia Iasonos
    •  & John O'Quigley

  • News & Views |

    An analysis of reports from phase III trials (published between 2011 and 2013) investigating patients with solid tumours found widespread failings in both the conduct and reporting of subgroup analyses. Readers might well be misled by such analyses. Editors should, therefore, implement policies to reduce the risk of publishing misleading results.

    • Douglas G. Altman

  • Review Article |

    Tumour-promoting inflammation is an enabling characteristic of many cancers. Conversely, many cancers can cause inflammation. Inflammation in the tumour microenvironment arises from the interplay of many different inflammatory cells and mediators, many of which are potential treatment targets. Herein, the authors review our current knowledge of the interplay between inflammation and tumorigenesis and discuss the potential of treatments that target cancer-related inflammation.

    • Shanthini M. Crusz
    •  & Frances R. Balkwill

  • Review Article |

    Liver cancer mortality has increased in the past 20 years, and estimates indicate that the global health burden of this disease will continue to grow. Advances in our knowledge of the human genome have provided a comprehensive picture of commonly mutated genes in patients with hepatocellular carcinoma (HCC). In this Review, the authors summarize the molecular concepts of progression of HCC, discuss the potential reasons for clinical trial failure, and propose new concepts of drug development.

    • Josep M. Llovet
    • , Augusto Villanueva
    •  & Richard S. Finn

  • Review Article |

    Immunoconjugates are specific, effective, minimally toxic anticancer therapies. They allow the delivery of a range of different effectors, including pharmacologic agents, radioisotopes, and toxins, to cancer cells. Of note, highly cytotoxic anticancer molecules could be linked to specific antibodies, which mask the toxic effects of the drug until it reaches its target. This Review summarizes the successes and shortcomings of immunoconjugates, and discusses the future potential for these therapies.

    • Brandon G. Smaglo
    • , Dalal Aldeghaither
    •  & Louis M. Weiner

  • 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

  • News & Views |

    The marriage of medicinal chemistry, molecular biology and medicine is perhaps best exemplified by the evolution of selective oestrogen-receptor modulators (SERMs). Translational studies might be useful for predicting the myriad clinical responses to SERMs, contributing to improvements in women's health.

    • V. Craig Jordan

  • Review Article |

    Highly efficacious vaccines are available to protect against persistent human papillomavirus (HPV) infection and, therefore, the associated neoplasias (most notably cervical cancer). This Review article discusses the two approved vaccines in terms of their structure, mode of action, efficacy, cross-reactivity with non-vaccine HPV types, safety and use in vaccination programmes.

    • Matti Lehtinen
    •  & Joakim Dillner

  • Review Article |

    With increasing numbers of anticancer drugs requiring testing, new adaptive model-based phase I trial designs can improve on current practice by exploring a wider range of dose combinations than standard phase I methods. In this Review, the authors describe the methods available as well as the opportunities and challenges faced in dual-agent phase I trials.

    • Jennifer A. Harrington
    • , Graham M. Wheeler
    •  & Duncan I. Jodrell

  • Review Article |

    Agents targeting the PI3K/AKT/mTOR pathway have been shown to be safe and effective in treating a number of tumour types. This Review outlines the background to these inhibitors and discusses the second-generation inhibitors of this pathway. The authors propose that the way forward for the development of inhibitors of the PI3K/AKT/mTOR pathway might be a systems biology approach and biomarker-driven studies.

    • Jordi Rodon
    • , Rodrigo Dienstmann
    •  & Josep Tabernero

  • Review Article |

    Combination strategies of molecular-targeted agents (MTAs) are being used in the hope of optimizing antitumour efficacy and to minimize the development of resistance, but very little effort is focused on molecular vulnerabilities of normal tissues. This Review discusses the main toxicities and the lack of tolerability of some common MTA combinations, and highlights what steps can be introduced for new preclinical testing paradigms for the assessment of chronic toxicities.

    • Sook Ryun Park
    • , Myrtle Davis
    •  & Shivaani Kummar

  • Year in Review |

    In 2012, we increased our knowledge of the molecular portrait of breast cancer. The BOLERO-2 and CLEOPATRA trials led to the approval of everolimus and pertuzumab; and the EMILIA trial will likely result in the approval of T-DM1. Some of these findings represent a paradigm shift in the way we think about the biology and management of breast cancer.

    • Mariana Chavez-MacGregor
    •  & Ana Maria Gonzalez-Angulo

  • News & Views |

    A phase II trial comparing dual MAPK pathway inhibition by combining BRAF and MEK inhibitors with BRAF inhibition alone showed increased progression-free survival and reduced incidence of secondary malignancies in patients with mutant BRAF V600 melanoma. This trial provides strong support for developing combinations hitting the same pathway in melanoma.

    • Keiran S. M. Smalley
    •  & Vernon K. Sondak

  • Review Article |

    Tumour dormancy is when cancer sleeps undetected for periods that can last up to decades. The therapeutic potential of inducing or maintaining this dormant period is clear. This Review describes the mechanisms of dormancy and uses genitourinary cancers as models to demonstrate how dormancy principles could be exploited clinically.

    • Jonathan A. Hensel
    • , Thomas W. Flaig
    •  & Dan Theodorescu

  • News & Views |

    The large randomized study by Crook et al. demonstrated that intermittent administration of androgen deprivation therapy should be considered the standard of care when patients with moderate and well-differentiated localized prostate cancer are treated for rising PSA levels after definitive radiotherapy.

    • Timur Mitin
    • , Jason A. Efstathiou
    •  & William U. Shipley

  • News & Views |

    The VELOUR and VITAL studies recently demonstrated ziv-aflibercept improved overall survival in patients with metastatic colorectal cancer (mCRC), including those previously treated with bevacizumab, but did not improve overall survival in non-small-cell lung cancer. Thus, VEGF-directed agents might be useful throughout the continuum of care in mCRC, but biomarkers are needed to identify patients likely to benefit.

    • Jeffrey M. Clarke
    •  & Herbert I. Hurwitz

  • News & Views |

    An update of the COU-AA-301 study confirms a survival advantage with abiraterone–prednisone compared to prednisone in post-docetaxel patients with metastatic castration-resistant prostate cancer. We place these data in the context of earlier disease states and other novel agents and explore practical issues concerning the future use of abiraterone.

    • Oliver Sartor
    •  & Sumanta K. Pal

  • Perspectives |

    PET or SPECT, is that the question? Single-photon emission computed tomography (SPECT) and positron emission tomography (PET) are both tomographic techniques that enable 3D-localization of the tumour and can be combined with CT for hybrid imaging; but is one better that the other? In oncology imaging nothing is black or white, and Rod Hicks and Michael Hofman provide us with an in-depth analysis of the advantages and disadvantages of each technique.

    • Rodney J. Hicks
    •  & Michael S. Hofman

Browse broader subjects

Browse narrower subjects

Browse Drug discovery across other nature.com journals