Articles in 2021

Prognostication of outcome across multiple cancers and prediction of response to various treatment modalities are among the next generation of challenges that artificial intelligence (AI) tools can solve using radiology images. The authors of this Perspective describe the evolution of AI-based approaches in oncology imaging and address the path to their adoption as decision-support tools in the clinic.

A high tumour burden has long been associated with inferior outcomes on traditional cancer therapies and emerging evidence suggests that tumour burden is particularly relevant for patients receiving immune-checkpoint inhibitors. Here, the authors summarize the available clinical and preclinical evidence for the role of tumour burden in determining the outcomes of patients receiving immune-checkpoint inhibitors and highlight areas that are likely to be of future research interest in this emerging area.

Chimeric antigen receptor (CAR) T cells have remarkable efficacy in patients with B cell acute lymphoblastic leukaemia (ALL), but have not been successful to date in patients with T cell ALL (T-ALL). Now, data from Pan and colleagues demonstrate the safety and impressive short-term efficacy of allogeneic donor-derived anti-CD7 CAR T cells in an early-phase clinical trial involving patients with relapsed and/or refractory T-ALL.

Immune-checkpoint inhibitors have dramatically improved the outcomes in patients with advanced-stage cancers, although the majority of patients will not respond to these agents. Here, the authors describe the potential of targeting emerging immunomodulatory pathways, with a focus on alternative immune checkpoints and tumour metabolism as approaches that might enable further improvements in the outcomes of patients with cancer, either as monotherapies or in combination with existing agents.

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.

Legislators in the USA have been discussing reforms to reduce the high cost of brand-name drugs, which are much higher in the USA than in other industrialized countries. One solution is to actively negotiate prices based on drugs’ clinical benefits. We discuss two important complexities from such an approach: drugs that have been approved for multiple indications and as part of a combination regimen.

Two recent studies addressed the functional properties and clinical significance of tumour antigen-specific effector T cells in human melanomas and lung carcinomas using single-cell strategies. Herein, we discuss their findings, which expand our understanding of T cell alterations in the tumour microenvironment and demonstrate that CD8⁺ T cell exhaustion is mediated by exposure to tumour cell-specific antigens and is associated with a tissue-resident memory phenotype.

Recent FDA draft guidance for sponsors of oncology clinical trials encourages enrolment of patients with incurable cancer and no potential for prolonged and/or near-normal survival, regardless of whether they have received existing treatment options. This guidance constitutes a substantial departure from current standards, with potentially profound implications for trial participants as well as drug regulation and reimbursement.

The MYC proto-oncogenes are among the most commonly activated proteins in human cancer, yet the clinical efficacy of MYC-targeted agents remains to be demonstrated. The authors of this Review describe how activation of the MYC pathway affects cancer cells as well as the tumour microenvironment and propose strategies for the therapeutic targeting of MYC-driven cancers.

Fluorescence-guided surgery (FGS) using tumour-targeted imaging agents has emerged over the past decade as a method of intraoperative cancer detection; however, the clinical implementation of tumour-targeted FGS remains in the early stages. The authors of this Review discuss how target selection, imaging agents and detection systems could enable real-time intraoperative visualization to benefit patients with cancer.