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FLASH radiotherapy involves delivering ultra-high dose rates of radiation, which enables sustained tumour control with reduced toxicity to surrounding tissues. The authors of this Perspective describe the principles underlying FLASH radiotherapy, present the available evidence from preclinical studies testing this modality and discuss the challenges for its application in routine clinical practice.
Glioblastoma, the most common form of brain cancer in adults, has a dismal prognosis and has proven recalcitrant to novel targeted therapies and immunotherapies. Extrachromosomal DNAs (ecDNAs) harbouring oncogenes are increasingly recognized as important drivers of tumour development, evolution and resistance to treatment, particularly in patients with glioblastoma. In this Perspective, the authors summarize key reasons for the failed clinical translation of new therapies for glioblastoma, highlighting the important contributions of ecDNAs. They then focus on the opportunities and challenges of utilizing ecDNAs to improve the likelihood of success in the development of precision medicines for this disease.
Liquid biopsy assays of diverse cancer-associated molecular alterations in blood, including genomic, epigenomic, transcriptomic, proteomic and metabolomics changes, offer considerable opportunities for early detection of cancer as well as improved management of the disease. In this Perspective, the authors review key advances in liquid biopsy-based multi-omics approaches for biomarker discovery. They also introduce the ‘nano-omics’ paradigm, whereby nanotechnology tools are used to capture and enrich various cancer-derived analytes from biofluids for subsequent omics analyses, with the aim of developing novel biomarker panels for early cancer detection.
In this Perspective, Nathan Cherny appraises the FDA approvals of therapeutic agents granted for use in adult patients with solid tumours during the 5 years 2017–2021 against the aspirations of the Cancer Moonshot, in terms of sheer number of approvals, the strength of the supporting evidence and the magnitude of clinical benefit. He also outlines areas where improvements are needed to more confidently ensure that the clinical benefits of approved treatments justify the associated risks.
Immune-checkpoint inhibitors are associated with a unique spectrum of organ-specific inflammatory toxicities known as immune-related adverse events (irAEs). In the past few years, aggregate clinical data, real-world data and multi-omics data have been used to investigate the underlying mechanisms and clinical presentations of irAEs. The authors of this Perspective summarize the knowledge on irAEs that has been obtained from different sources of ‘big data’.
