Molecular medicine articles within Nature Reviews Clinical Oncology

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  • Review Article |

    According to the precision oncology paradigm, cancer therapies are increasingly being matched to specific sensitizing alterations using a biomarker-directed approach. However, the criteria for determining the actionability of molecular alterations and selecting matched treatments evolve over time. Molecular tumour boards (MTBs) have emerged as means to capitalize on the collective knowledge of various experts to interpret molecular-profiling data and to eliminate subjectivity in treatment selection. This Review describes the components, processes and increasingly important role of MTBs in optimizing the implementation of precision oncology in both clinical trials and clinical practice, as well as current and future considerations for ensuring the sustainability of MTBs and expanding their outreach to underserved populations.

    • Apostolia M. Tsimberidou
    • , Michael Kahle
    •  & Funda Meric-Bernstam

  • Review Article |

    Lung cancers harbouring ‘rare’ alterations (defined as those with a prevalence of <5% of oncogene-driven lung cancers) can be detected in around a third of all oncogene-driven lung cancers and are diagnosed in thousands of patients each year. Advances in our understanding of tumour biology, diagnosis and the development of novel therapies are enabling increasing use of specific therapies targeting these alterations. In this Review, the authors provide an overview of the epidemiology, diagnosis, prognosis and treatment of patients with lung cancers harbouring these rare alterations. The importance of expedited drug approval pathways and cooperation between multiple stakeholders is also emphasized.

    • Guilherme Harada
    • , Soo-Ryum Yang
    •  & Alexander Drilon

  • Review Article |

    Protein degraders constitute a new class of agents that eliminate, rather than just inhibit, their target proteins. These novel agents have recently entered testing in oncology trials, with initial data providing clinical proof of concept for the mechanism of action as well as the antitumour activity of heterobifunctional protein degraders. In this Review, the authors outline the progress in the development of such protein degraders for the treatment of cancer and consider prospects and potential challenges for these agents.

    • Deborah Chirnomas
    • , Keith R. Hornberger
    •  & Craig M. Crews

  • News & Views |

    A high tumour mutational burden (≥10 mutations per megabase) is a companion biomarker in the histology-agnostic approval of pembrolizumab for treatment-refractory advanced-stage solid tumours, and continues to be an exploratory predictive biomarker for immune-checkpoint inhibitors in non-small-cell lung cancer. Herein, we discuss recent results from the first phase III trial evaluating blood-based tumour mutational burden in patients with treatment-naive advanced-stage non-small-cell lung cancer.

    • So Yeon Kim
    •  & Roy S. Herbst

  • Perspective |

    Liquid biopsy assays have the potential to revolutionize the diagnosis and management of cancer, and rapid progress is being made in the clinical translation of such assays. This Perspective outlines notable advances in the use of liquid biopsy technologies in the management of solid tumours, as well as future research avenues, clinical trial methodologies and implementation logistics for the eventual integration of liquid biopsy into the clinical workflow.

    • Michail Ignatiadis
    • , George W. Sledge
    •  & Stefanie S. Jeffrey

  • Comment |

    As more patients with oncogene-driven non-small-cell lung cancer are treated with targeted therapies, they are joining forces online to form groups that provide support, education and advocacy focused on specific oncogenes. Herein, we discuss how the involvement of these groups in patient-partnered research can benefit both patients and lung cancer research.

    • Merel Hennink
    • , Geert Vandeweyer
    •  & Janet Freeman-Daily

  • News & Views |

    The biological complexity of triple-negative breast cancers (TNBCs) and the lack of highly recurrent targetable genetic alterations pose major challenges for the implementation of targeted therapies for this disease. A recent multiomic in silico study has identified genetic drivers of five different TNBC molecular subtypes, providing new opportunities for precision medicine approaches.

    • Fresia Pareja
    •  & Jorge S. Reis-Filho

  • News & Views |

    The success of cancer therapies is hampered by a paucity of suitable drug targets and the rapid development of therapy resistance. The concept of synthetic lethality provides a potential solution to these constraints via the identification of novel therapeutic vulnerabilities, as exemplified in two recent studies.

    • Diede Brunen
    •  & René Bernards

  • Review Article |

    Analysis of circulating tumour components using liquid biopsy approaches holds considerable promise to improve the detection and treatment of cancer. In this Review, Alberto Bardelli and colleagues outline how different forms of liquid biopsy, and particularly the assessment of circulating tumour DNA, can be exploited to guide patient care, and discuss the progress made to date in integrating such analyses into the clinic.

    • Giulia Siravegna
    • , Silvia Marsoni
    •  & Alberto Bardelli

  • News & Views |

    Data from the recent Stop 2G-TKI study confirm that around 60% of patients with chronic myeloid leukaemia who discontinue second-generation BCR–ABL1 tyrosine-kinase inhibitor (TKI) therapy after a sustained deep molecular response remain in remission for longer than 1 year. Importantly, the interim findings suggest that prior response to first-line TKI treatment might predict relapse risk after treatment discontinuation.

    • Timothy P. Hughes
    •  & David M. Ross

  • Opinion |

    Telomerase reverse transcriptase (TERT) is expressed constitutively in tumour cells throughout the evolution of many cancers; therefore, this potential tumour self-antigen has been an important target for anticancer vaccines over the past 10 years, but only modest benefits from this approach have been observed in clinical trials. In this Perspectives, Maurizio Zanetti reviews these studies, and highlights advances in our knowledge that warrant further development and refinement of TERT immunotherapy.

    • Maurizio Zanetti

  • Review Article |

    Advances in our understanding of thyroid cancer biology have led to the regulatory approval of a number of molecularly targeted therapies for advanced-stage disease. Herein, the authors summarize the progress made to date in molecular medicine for the different histotypes of thyroid cancer, and highlight the questions for future research focused on treatment of the various disease subtypes.

    • Keith C. Bible
    •  & Mabel Ryder

  • News & Views |

    A recent study has demonstrated that serial profiling of resistance mutations in cell-free DNA (cfDNA) collected from the blood of patients with colorectal cancer can be used to track tumour evolution throughout the therapeutic course. This approach has the potential to inform personalized medicine by enabling dynamic adaptation of therapy.

    • Samra Turajlic
    •  & Charles Swanton

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