Cell biology articles within Nature Reviews Clinical Oncology

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  • Review Article |

    The entry of cells into senescence can act as a barrier to tumorigenesis; however, in certain contexts senescent malignant and non-malignant cells can acquire pro-tumorigenic properties. The authors of this Review discuss the cell-intrinsic and cell-extrinsic mechanisms involved in both the antitumorigenic and tumour-promoting roles of senescent cells, and describe the potential of various senolytic and senomorphic therapeutic approaches in oncology.

    • Clemens A. Schmitt
    • , Boshi Wang
    •  & Marco Demaria

  • 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 |

    The authors of this Review present the main pathways that regulate apoptosis as well as other signalling pathways that interact with them, highlighting actionable molecular targets for anticancer therapy. They also provide an overview of therapeutic agents exploiting apoptosis currently in clinical translation and known mechanisms of resistance to these agents.

    • Benedito A. Carneiro
    •  & Wafik S. El-Deiry

  • Review Article |

    Lineage plasticity is a source of intratumoural heterogeneity and enables tumour adaptation to an adverse tumour microenvironment, eventually leading to therapeutic resistance. The authors of this Review provide an overview of the impact of lineage plasticity on cancer progression and therapy resistance, with a focus on neuroendocrine transformation in lung and prostate tumours, and discuss emerging management strategies and open questions in the field.

    • Álvaro Quintanal-Villalonga
    • , Joseph M. Chan
    •  & Charles M. Rudin

  • Perspective |

    The oligometastatic paradigm challenges the prevailing view of metastasis as a disseminated process and proposes the existence of a spectrum of biological virulence within metastatic lesions. The authors present evidence for this heterogeneity and discuss how it affects the staging and treatment of patients with metastatic cancer.

    • Sean P. Pitroda
    •  & Ralph R. Weichselbaum

  • Review Article |

    Effective therapeutic strategies to target RAS-mutant cancers have proved elusive, but in the past few years, several promising strategies have been tested in clinical trials. The authors describe historical and ongoing therapeutic approaches based on the direct or indirect targeting of RAS.

    • Meagan B. Ryan
    •  & Ryan B. Corcoran

  • Review Article |

    The tumour stroma is a component of the tumour microenvironment and has crucial roles in tumour initiation, progression, and metastasis. Most anticancer therapies target cancer cells specifically, but the tumour stroma can promote resistance to such therapies. Herein, the authors provide an overview of the complex cancer cell–tumour stroma interactions and discuss how novel treatment strategies should combine anticancer and antistromal agents.

    • Kenneth C. Valkenburg
    • , Amber E. de Groot
    •  & Kenneth J. Pienta

  • Review Article |

    The interleukin-6 (IL-6)/Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathway is aberrantly hyperactivated in many types of cancer, and such hyperactivation is generally associated with a poor clinical prognosis. In this Review, the authors describe the clinical potential of agents designed to inhibit the IL-6/JAK/STAT3 signalling pathway, either alone or in combination with other agents, in patients with cancer.

    • Daniel E. Johnson
    • , Rachel A. O'Keefe
    •  & Jennifer R. Grandis

  • Review Article |

    Aberrant chromosomal architecture is one of the most common features of cancer and can often lead to chromosomal instability (CIN). In this Review, the authors describe the role of CIN in the development and progression of cancer and the potential to target the therapeutic vulnerabilities created by this process.

    • Laurent Sansregret
    • , Bart Vanhaesebroeck
    •  & Charles Swanton

  • Review Article |

    Clinical trials are an essential aspect of drug development; however, in patients with non-castrate prostate cancer, the long natural history of the disease provides a major barrier to the introduction of new therapies. In this Review, the authors describe the potential of a novel, multi-arm, multistage, clinical trial project, with surrogate end points designed to fully reflect the effects of treatments, in transforming the treatment of patients with early stage prostate cancer, before the development of castration-resistant disease.

    • Min Yuen Teo
    • , Matthew J. O'Shaughnessy
    •  & Howard I. Scher

  • 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

  • Opinion |

    Autophagy is fundamental to cellular homeostasis and also has a central role in the development and progression of cancer. However, autophagy is also required for optimal immune system function, including the development of an anticancer immune response. In this Perspective, the authors present the available preclinical and clinical evidence that autophagy might enhance the effectiveness of both immunogenic chemotherapy and radiotherapy, as opposed to the general view of inhibition of autophagy as an antitumour strategy.

    • Lorenzo Galluzzi
    • , José Manuel Bravo-San Pedro
    •  & Guido Kroemer

  • Review Article |

    Distant metastasis remains a common cause of death in patients with solid tumours, even after treatment with surgery, radiotherapy and/or chemotherapy. Treatment itself can sometimes cause or promote metastasis by increasing the number of circulating tumour cells. The authors of this article discuss preclinical and clinical data concerning cancer treatments, circulating tumour cell mobilization and other factors that might promote metastasis.

    • Olga A. Martin
    • , Robin L. Anderson
    •  & Michael P. MacManus

  • Review Article |

    Metronomic chemotherapy regimens were developed to optimize the antitumour efficacy of antiangiogenic agents and to reduce toxicity of antineoplastic drugs, but the effectiveness of this approach also relies on other mechanisms, such as the stimulation of the immune system. Investigating the pharmacokinetic and pharmacodynamic properties of agents administered in metronomic regimens will enable a more-personalized therapeutic approach. Herein, Bocci and Kerbel discuss results from early phase and pilot clinical studies that support the important link between pharmacokinetics and metronomic chemotherapy.

    • Guido Bocci
    •  & Robert S. Kerbel

  • Review Article |

    Aberrant cellular proliferation is a hallmark of cancer, and the activation of cyclin-dependent kinases (CDKs) is a key feature of this proliferation. In this Review, the authors describe the biological rationale for targeted inhibition of CDK4/6, review the available clinical evidence for the agents that are in clinical development, and discuss the challenges with regard to optimizing their use.

    • Ben O'Leary
    • , Richard S. Finn
    •  & Nicholas C. Turner

  • 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

  • News & Views |

    Two novel agents targeting the androgen receptor signalling axis, even after chemotherapy treatment, have been demonstrated to be effective in patients with metastatic castration-resistant prostate cancer (CRPC). Enzalutamide is the newest approved treatment that improves survival in this lethal and morbid disease.

    • Che-Kai Tsao
    •  & William K. Oh

  • Opinion |

    Patients with metastatic disease are usually treated initially with systemic therapy alone. Morgan and Parker review clinical data suggesting that the local treatment of the primary tumor might retard progression of distant metastases, making the case for the conduct of more randomized clinical trials that investigate this hypothesis.

    • Scott C. Morgan
    •  & Chris C. Parker

  • Review Article |

    Antiangiogenic therapy is thought to starve tumors by cutting their nutrient and oxygen supply. The authors review evidence for a potential link between hypoxia signaling and an invasive switch that occurs in cancer cells, through which antiangiogenic drugs could increase the risk of tumor metastasis in certain conditions, and discuss approaches to reduce tumor dissemination.

    • Katrien De Bock
    • , Massimiliano Mazzone
    •  & Peter Carmeliet

  • Review Article |

    Autophagy is an important cellular recycling mechanism that can be either tumor-promoting or tumor-suppressive and represents a novel anti-cancer target. In this article, Janku and colleagues explain the rational behind targeting autophagy for the development of anticancer therapy and discuss drugs that either inhibit or activate autophagy.

    • Filip Janku
    • , David J. McConkey
    •  & Razelle Kurzrock

  • 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

  • Review Article |

    Circulating tumor cells (CTCs) have a crucial role in the metastatic cascade, tumor dissemination and progression. Furthermore, CTCs are involved in treatment failure, therapy resistance and disease progression. New therapeutic possibilities are offered by the established clinical prognostic and predictive value of CTCs with the additional possibility of using them for the real-time monitoring of systemic-therapy efficacy. This Review discusses the future clinical applications of CTCs in breast cancer including the incorporation of CTCs as end points in clinical trials and the blockade of tumor dissemination and self seeding via the therapeutic targeting of CTCs.

    • Michal Mego
    • , Sendurai A. Mani
    •  & Massimo Cristofanilli

  • Review Article |

    Castleman's disease is an infectious disease of the lymph node that causes either local symptoms or a systemic inflammatory syndrome. This Review discusses the viral causes of the disease and the mechanisms of its subsequent progression. The efficacy of established treatment options for this disease and of potential novel therapies is outlined.

    • Klaus-Martin Schulte
    •  & Nadia Talat

  • Review Article |

    Survival outcomes for advanced or metastatic non-small-cell lung cancer remain poor; however, molecular targeted agents offer new opportunities provided that patients are selected for treatment according to their tumor profile. This Review highlights the promising activity shown with novel targeted therapies that interfere with the IGF-1R pathway and agents that inhibit the EML4-ALK fusion protein. Aberrations in other key signaling pathways that have been identified as crucial targets, especially in resistant patients, are also discussed.

    • Filip Janku
    • , David J. Stewart
    •  & Razelle Kurzrock

  • 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

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