Skin cancer articles within Nature Reviews Clinical Oncology

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  • Review Article |

    Various BRAF alterations are found and function as oncogenic drivers across diverse cancer types. BRAF inhibitor-based therapy has improved outcomes for patients with cancers harbouring BRAFV600 mutations, although resistance develops in most, and the current inhibitors are not effective against other types of BRAF alterations. In this Review, the authors describe the mechanisms underlying oncogenic BRAF signalling, as well as pan-cancer and lineage-specific mechanisms of intrinsic, adaptive and acquired resistance to BRAF inhibitors. They also discuss novel RAF inhibitors and drug combinations designed to overcome these resistance mechanisms and/or expand the applicability of molecularly targeted therapy to a broader range of BRAF-mutant cancers.

    • Aphrothiti J. Hanrahan
    • , Ziyu Chen
    •  & David B. Solit

  • Review Article |

    Despite dramatic progress over the past decade, only around 50% of patients with advanced-stage melanoma derive durable benefit from immune-checkpoint inhibitors (ICIs) and/or BRAF and MEK (BRAF/MEK) inhibitors. Over the past few years, adoptive cell therapy with tumour-infiltrating lymphocytes (TILs) has demonstrated encouraging efficacy including in patients with disease progression on ICIs or BRAF/MEK inhibitors. In this Review, the authors summarize the role of TIL therapies in the management of these patients and describe future research strategies that might improve safety or efficacy.

    • Sebastian Klobuch
    • , Tom T. P. Seijkens
    •  & John B. A. G. Haanen

  • Review Article |

    Neoadjuvant immune-checkpoint inhibition is a promising emerging treatment strategy that potentially enables patients with a good response to initial therapy to avoid further treatment and the associated toxicity risks, while also identifying those who might require treatment escalation. In this Review, the authors describe treatment personalization strategies based on the initial response to one or more neoadjuvant immune-checkpoint inhibitors and consider the potential to expand this approach beyond patients with melanoma.

    • Minke W. Lucas
    • , Judith M. Versluis
    •  & Christian U. Blank

  • Review Article |

    Oncolytic viruses (OVs) provide a novel cancer treatment strategy, with a mechanism of action and toxicity profiles that are distinctly different to those of more traditional therapies. Thus far, four OVs have entered clinical use globally, yet only talimogene laherparepvec (T-VEC) has entered widespread clinical use. In this Review, the authors describe the clinical and regulatory experience with T-VEC thus far, and how this can guide the development of novel OVs. Discussions of a range of novel OVs with the potential for clinical implementation in the near future are also provided.

    • Sophia Z. Shalhout
    • , David M. Miller
    •  & Howard L. Kaufman

  • Review Article |

    Although almost all patients with uveal melanoma have localized disease at diagnosis, and despite effective treatment of the primary tumour, metastatic recurrence is common and holds a dismal prognosis. Unlike its cutaneous counterpart, therapeutic advances for uveal melanoma have not been forthcoming, although the recent approval of the first systemic therapy for this disease has ushered in a new era of hope. This Review summarizes the biology of uveal melanoma and the management of primary disease, including molecular risk classification, adjuvant therapy and follow-up strategies. The discussion is then focused on the established and emerging regional and systemic treatments for metastatic uveal melanoma.

    • Richard D. Carvajal
    • , Joseph J. Sacco
    •  & Sophie Piperno-Neumann

  • News & Views |

    Clinical trials of neoadjuvant therapy for melanoma have expanded rapidly over the past several years. Preliminary data demonstrate the prognostic value of pathological response, which might have clinical implications for refining the roles of surgery and adjuvant therapy. These clinical questions are under active investigation across many ongoing clinical trials.

    • Giorgos C. Karakousis
    •  & Tara C. Mitchell

  • Viewpoint |

    Immune-checkpoint inhibitors and BRAF-targeted therapy have revolutionized the treatment of advanced-stage, unresectable melanoma and have been successfully transitioned into the resectable disease setting as (neo)adjuvant treatments. The expanding range of treatment options available for resectable high-risk melanoma raises questions over selection of the optimal therapeutic strategy and agents for each individual. Furthermore, the use of perioperative therapy has potentially important implications for the management of patients who have disease recurrence. In this Viewpoint, we asked four expert investigators who have been involved in the key studies of perioperative systemic therapies for their perspectives on the optimal management of patients with high-risk melanoma.

    • Alexander M. M. Eggermont
    • , Omid Hamid
    •  & Jason J. Luke

  • News & Views |

    Two recent large-cohort studies reinforce the potential predictive capability of gut microbiota for immune-checkpoint inhibitor response and toxicities in patients with melanoma. However, additional investigations are required to understand the mechanistic underpinnings of this complex multifaceted relationship, and how it can be exploited for personalized cancer care.

    • Neal Bhutiani
    •  & Jennifer A. Wargo

  • Review Article |

    Photoacoustic imaging is a novel imaging technique that provides scalably high levels of spatial resolution at rapid acquisition speed, without the need for radiation or exogenous contrast agents. In this Review, the authors describe the emerging role of this technology in the screening, diagnosis and management of patients with cancer, and provide an overview of the future implementation of this technology.

    • Li Lin
    •  & Lihong V. Wang

  • Review Article |

    Immune-checkpoint inhibitors (ICIs) have dramatically improved the outcomes of patients with advanced-stage solid tumours, including the potential for long-term remission in a subset. However, long-term follow-up data reveal a risk of chronic toxicities from these agents, which can have important quality-of-life implications. In this Review, the authors describe the current level of evidence of chronic toxicities of ICIs and their implications for patients

    • Douglas B. Johnson
    • , Caroline A. Nebhan
    •  & Justin M. Balko

  • News & Views |

    An unfavourable gut bacterial composition has been shown to reduce the likelihood of clinical benefit from immune-checkpoint inhibitors (ICIs). The results of two first-in-human studies of faecal microbiota transplantation in patients with melanoma refractory to anti-PD-1 antibodies validate preclinical evidence that this approach can improve the gut microbiota and overcome resistance to ICIs; however, many questions remain.

    • Arielle Elkrief
    •  & Bertrand Routy

  • News & Views |

    Tumour-associated antigens are an attractive therapeutic target in immuno-oncology. Here, the exploratory analyses of T cell responses and preliminary clinical outcomes of the Lipo-MERIT trial of a melanoma vaccine are discussed in the context of prior efforts to harness the immunogenicity of such antigens for antitumour immunity.

    • Anjali Rohatgi
    •  & John M. Kirkwood

  • News & Views |

    Liu et al. report data from the largest sequencing analysis of tumour material from patients with metastatic melanoma receiving immune-checkpoint inhibitors. These data confirm the correlations between baseline immune infiltrate and treatment response, but also demonstrate inconsistent associations of tumour mutational burden, specific gene mutations and previously described gene expression patterns with clinical outcomes.

    • Jason J. Luke
    •  & Paolo A. Ascierto

  • Review Article |

    Immune-checkpoint inhibitors (ICIs) have dramatically improved the survival of patients with certain forms of cancer; however, these agents also have adverse effects that are often quite different to those of more traditional cancer therapies. In this Review, the authors describe the epidemiology, treatment and management of the various immune-related adverse events that can occur in patients receiving ICIs.

    • Filipe Martins
    • , Latifyan Sofiya
    •  & Michel Obeid

  • Consensus Statement
    | Open Access

    Merkel cell carcinoma (MCC) is a rare and aggressive form of nonmelanoma skin cancer. The availability of immune checkpoint inhibition has improved the outcomes of a subset of patients with MCC, although many unmet needs continue to exist. In this Consensus Statement, the authors summarize developments in our understanding of MCC while also providing consensus recommendations for future research.

    • Paul W. Harms
    • , Kelly L. Harms
    •  & Isaac Brownell

  • News & Views |

    New treatment options for patients with resected stage III melanoma have been established with the publication of the results of four pivotal randomized clinical trials, resulting in three drug approvals, with a forth expected, all within only 4 years. Herein, we put these advances into context.

    • Alexander M. M. Eggermont
    • , Caroline Robert
    •  & Antoni Ribas

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