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  • Around 100 new cancer drugs, defined as new molecular entities, were approved in China between 2005 and 2021. More than half of these new cancer drugs do not constitute innovations in mechanism of action or therapy and do not have documented meaningful clinical benefit. Approaches are needed to promote meaningful innovation for patients with cancer.

    • Yichen Zhang
    • Anita K. Wagner
    • Xiaodong Guan
  • Caring for individuals with thyroid nodules requires accurate estimation of their risk of thyroid cancer; however, available diagnostic tools offer only imprecise estimates. Novel biomarkers might help to clarify thyroid cancer risk and facilitate more-accurate diagnostic decision-making, although limitations in this area continue to exist.

    • Naykky Singh Ospina
    • Juan P. Brito
    News & Views
  • Immune-checkpoint inhibitors (ICI) constitute a paradigm shift in the treatment of non-small-cell lung cancer (NSCLC); however, identifying the minority of patients who derive long-term benefit remains problematic, particularly among those with targetable oncogenic drivers who have typically been under-represented in or excluded from clinical trials of ICIs. This Review summarizes the associations of common oncogenic drivers of NSCLC with sensitivity or resistance to ICIs as well as the underlying effects on the immune tumour microenvironment. Potential vulnerabilities that could potentially be exploited to overcome primary resistance to ICIs conferred by certain oncogenic drivers are also highlighted.

    • Itziar Otano
    • Alvaro C. Ucero
    • Luis Paz-Ares
    Review Article
  • Preclinical models that faithfully recapitulate interactions between the human immune system and tumours are necessary to evaluate human-specific immunotherapies in vivo; however, their number is currently limited. The authors of this Review discuss the currently available humanized mouse models, which are immunodeficient mice co-engrafted with human tumours and immune components, with a focus on their applicability in translational research.

    • Jane Chuprin
    • Hannah Buettner
    • Michael A. Brehm
    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
  • New genetic analyses demonstrate that the presence of low-frequency subclonal populations, including high-risk subclones, at diagnosis in multiple myeloma can contribute to disease relapse and poor clinical outcomes. Thus, sensitive detection approaches are required to detect these subclones at diagnosis together with innovative treatment strategies to eradicate low-frequency, high-risk subclones and prevent them from becoming dominant.

    • Eileen M. Boyle
    • Faith E. Davies
    News & Views
  • γδ T cells are lymphocytes with properties of both typical αβ T cell and natural killer cells, notable tissue tropisms, and MHC-independent antitumour functions that make them attractive agents for cancer immunotherapy. In this Review, the authors provide an overview of human γδ T cell subsets, discuss the antitumour and pro-tumour activities of these cells and their prognostic value in patients with cancer, and describe the current landscape of γδ T cell-based immunotherapies.

    • Sofia Mensurado
    • Rafael Blanco-Domínguez
    • Bruno Silva-Santos
    Review Article
  • Immunotherapies have dramatically improved the outcomes of a subset of patients with advanced-stage cancers. Nonetheless, most patients will not respond to these agents and adverse events can be severe. In this Review, the authors describe the potential to address these challenges by combining immunotherapies with currently available thermal therapies as well as by using thermal immuno-nanomedicines.

    • Zhe Yang
    • Di Gao
    • Xingcai Zhang
    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
    Review Article
  • Although radiotherapy affects multiple cellular pathways, treatments are generally planned with the assumption that all tumours respond similarly to radiation. The authors of this Review summarize the effect of various pathways activated by radiotherapy on tumour responses to radiotherapy and present the current knowledge on genomic classifiers designed to inform treatment decisions.

    • James M. Price
    • Asmithaa Prabhakaran
    • Catharine M. L. West
    Review Article
  • Despite a considerable increase in research output over the past decades, the translation of radiomic research into clinically useful tests has been limited. In this Review, the authors provide 16 key criteria to guide the clinical translation of radiomics with the hope of accelerating the use of this technology to improve patient outcomes.

    • Erich P. Huang
    • James P. B. O’Connor
    • Lalitha K. Shankar
    Review Article
  • PADA-1 is the first trial to demonstrate benefit from a treatment-switching strategy guided by active monitoring of ESR1 mutations in plasma circulating tumour DNA (ctDNA) from patients with breast cancer. The results of this trial raise important questions about the specific treatment approach tested, and the feasibility of trials incorporating longitudinal ctDNA analyses to anticipate resistance and guide treatment.

    • Ben O’Leary
    News & Views
  • The first phase III trial to test perioperative immune-checkpoint inhibitor therapy for high-risk renal cell carcinoma yielded highly promising results, leading to regulatory approvals of adjuvant pembrolizumab. However, subsequent phase III trials, including the IMmotion010 trial of adjuvant atezolizumab, did not demonstrate similar benefits. Although molecular biomarkers are urgently needed to better delineate responder subgroups, the unique design of each trial might partially explain some of the patterns identified.

    • Chris Labaki
    • Toni K. Choueiri
    News & Views