Molecular biology articles within Nature Reviews Clinical Oncology

Featured

  • Review Article |

    In oncology, mRNA–lipid nanoparticles (LNPs) have been used either to achieve intratumoural expression of immune-stimulating cytokine combinations or as cancer vaccines, and new strategies are in development to enable the selective delivery of payloads into cancer cells previously considered unreachable. The authors of this Review present various approaches for delivering mRNA–LNPs to tumours and discuss improvements that will improve the selective targeting of cancer cells with mRNA–LNPs.

    • Edo Kon
    • , Nitay Ad-El
    •  & Dan Peer

  • Review Article |

    Targeted therapies have improved the outcomes of many patients with cancer, although many more lack targetable alterations or do not derive clinical benefit for other reasons. Radiotherapy can also provide benefit to many patients, although radioresistance often limits the effectiveness of this intervention. Here, the authors describe the potential for radiotherapy to promote non-oncogene dependence on targetable signalling pathways, thus extending the benefits of both targeted therapy and radiotherapy to greater numbers of patients.

    • Giulia Petroni
    • , Lewis C. Cantley
    •  & Lorenzo Galluzzi

  • Review Article |

    EGFR exon 19 deletions and exon 21 mutations, and HER2 amplification and/or overexpression, are predictive of response to matched molecularly targeted therapies that have greatly improved patient outcomes. However, insertion mutations in exon 20 of either EGFR or HER2 generally do not confer sensitivity to these therapies. In this Review, the authors discuss the prevalence of EGFR and HER2 exon 20 insertions across cancers, their biology and detection, and associated responses to current molecularly targeted therapies and immunotherapies. In addition, they focus on new therapeutic strategies that are being developed to target tumours driven by these non-classic EGFR and HER2 alterations.

    • Alex Friedlaender
    • , Vivek Subbiah
    •  & Alfredo Addeo

  • Review Article |

    Poly(ADP-ribose) polymerase (PARP) inhibitors are approved for patients with several forms of cancer, predominantly those harbouring loss-of-function BRCA1/2 mutations or other homologous recombination defects. Nonetheless, most patients receiving PARP inhibitors will ultimately develop resistance to PARP inhibitors, resulting in disease progression. In this Review, the authors describe the mechanisms of resistance to PARP inhibitors and discuss the potential treatment strategies that might overcome these effects.

    • Mariana Paes Dias
    • , Sarah C. Moser
    •  & Jos Jonkers

  • Review Article |

    Androgen receptor (AR) splice variants (AR-Vs) are truncated isoforms of the AR, of which a subset remain constitutively active in the absence of circulating androgens. AR-Vs have been proposed to contribute to therapeutic resistance. The authors of this Review outline the current understanding of the role of the spliceosome in prostate cancer progression and explore the therapeutic utility of manipulating alternative splicing.

    • Alec Paschalis
    • , Adam Sharp
    •  & Johann. S. de Bono

  • Review Article |

    Following the success of poly(ADP-ribose) PARP inhibitors in patients with BRCA1/2 mutations, considerable research interest has emerged in the discovery of alternative forms of synthetic lethality. In this Review, the authors summarize the potential of various novel forms of synthetic lethality to further improve the treatment of patients with cancer.

    • Alan Ashworth
    •  & Christopher J. Lord

  • Review Article |

    Evidence of the functional roles of non-coding RNAs in cancer is expanding, and the potential of these RNAs as diagnostic and prognostic biomarkers is increasingly recognized. Herein, the authors review the recent developments in these areas and provide compendiums of circulating microRNAs and long non-coding RNAs that have promise as diagnostic and prognostic cancer biomarkers.

    • Simone Anfossi
    • , Anna Babayan
    •  & George A. Calin

  • Review Article |

    The identification of the tissue of origin in patients with cancer of unknown primary (CUP) is an example of how epigenomics can be incorporated in clinical settings. Epigenetic and other molecularly-based diagnostic strategies have emerged to complement traditional diagnostic procedures, thereby improving the clinical management of patients with CUP. Herein, the authors present the latest data on strategies using epigenetics and other molecular biomarkers to guide therapeutic decisions involving patients with CUP, addressing a previously unmet need.

    • Sebastián Moran
    • , Anna Martinez-Cardús
    •  & Manel Esteller

  • Review Article |

    By preventing the accumulation of misfolded or damaged proteins, the ubiquitin-proteasome pathway has essential functions in cell homeostasis. Cancer cells produce proteins that promote cell survival and proliferation, and inhibit cell death, and thus, clinical trials have tested the therapeutic effect of proteasome inhibitors on patients with a variety of cancer types, mainly haematological malignancies. Herein, the authors discuss the advances and challenges derived from the introduction of proteasome inhibitors in the clinic, including therapeutic resistance.

    • Elisabet E. Manasanch
    •  & Robert Z. Orlowski

  • 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

  • Review Article |

    MicroRNAs (miRNAs) is an exciting and fast-moving field in cancer diagnosis and therapeutics. This Review highlights the use of circulating miRNAs in body fluids as a noninvasive diagnostic tool and as a treatment-response predictor. It also explores the concept that body-fluid-based miRNAs possibly originated as the first 'hormones'.

    • Maria Angelica Cortez
    • , Carlos Bueso-Ramos
    •  & George A. Calin

  • Review Article |

    The translation of mRNA is a tightly regulated process that is necessary for protein synthesis, and dysregulation of this process is associated with the development and progression of cancers. This Review highlights the components of translation machinery and how alterations in these proteins and their principle upstream signaling pathways can impact on cancer. Drugs that are currently being developed to target the translational machinery are also discussed.

    • Sarah P. Blagden
    •  & Anne E. Willis

  • Opinion |

    In this Perspective, the clinical disappointment of mitosis-specific agents is explained in the context of the mechanism of action of microtubule-targeting agents. The authors propose a new paradigm for the anticancer activity of microtubule-targeting agents and suggest that mitosis-specific inhibitors will not result in significant clinical impact.

    • Edina Komlodi-Pasztor
    • , Dan Sackett
    •  & Tito Fojo

  • Review Article |

    MicroRNAs (MiRNAs) can act as oncogenes or tumor-suppressor genes and have differential expression in tumor progression and metastasis. MiRNAs are involved in a number of pathways that contribute to metastasis, including migration, invasion, cell proliferation, epithelial-to-mesenchymal transition, angiogenesis and apoptosis. This Review provides a summary of the existing data documenting these functions and describes the clinical utility of miRNAs as prognostic and predictive biomarkers and their potential therapeutic applications in advanced cancer.

    • Nicole M. A. White
    • , Eman Fatoohi
    •  & George M. Yousef

  • Opinion |

    Defective DNA mismatch repair (MMR) occurs in approximately 15% of sporadic colorectal cancers. Studies have shown that patients with MMR-deficient colorectal cancers have a more favorable prognosis, but evidence indicates these patients do not benefit from adjuvant 5 fluorouracil-based chemotherapy. The importance of determining MMR status to inform clinical decision-making for adjuvant chemotherapy in patients with stage II colon cancer is discussed.

    • Frank A. Sinicrope

  • Review Article |

    Mutations in the mismatch repair (MMR) genes are associated with an increased risk of developing colorectal cancer (CRC). In this Review, the authors outline the MMR system and describe how defective MMR impacts on the management of CRC. The authors also discuss how targeting these mutations can be exploited in the development of novel therapeutic strategies.

    • Madeleine Hewish
    • , Christopher J. Lord
    •  & Alan Ashworth

  • Review Article |

    Microsatellite instability (MSI) is a frequent molecular phenomenon of colorectal cancer and is associated with deficient DNA mismatch repair. This Review presents an overview of MSI, including its clinical features and applications. The authors discuss the prognostic and predictive value of MSI and how it can be used to improve our knowledge of other cancer subtypes.

    • Eduardo Vilar
    •  & Stephen B. Gruber

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