Articles in 2021

Cerebrospinal fluid liquid biopsies can enable the characterization and monitoring of medulloblastoma. The analysis of copy-number variations in circulating tumour DNA present in these samples can be used as a biomarker to determine the presence of measurable residual disease, and facilitate the optimal treatment and clinical management of patients with medulloblastoma.

Circular RNAs (circRNAs) are a novel class of primarily non-coding RNAs with increasingly recognized roles in cancer development and progression through diverse mechanisms of action. Herein, the authors review the current understanding of circRNA biogenesis, regulation, physiological functions and pathophysiological roles in cancer. They also discuss the clinical potential of circRNAs as biomarkers, therapeutic agents and drug targets in oncology as well as research controversies, technical issues and biological knowledge gaps that need to be addressed before this promise can be realized.

Patients receiving cytotoxic therapies for cancer have an increased risk of cognitive and functional decline that is usually associated with ageing. In this Review, the authors describe how cancer therapies can enhance physiological ageing processes and highlight the potential for interventions that could potentially ameliorate these long-term adverse events in patients receiving active treatment for cancer and in cancer survivors.

In oncology, a definition of drug value that patients, payers, regulators and clinicians agree upon on does not exist. The authors of this Perspective discuss different approaches to measuring value, such as assessments of benefit–risk balance and cost-effectiveness, individual attitudes to risk, and use of scales developed to measure value objectively. They also explain how regulators can help to inform different decision makers.

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.

Daratumumab is an anti-CD38 monoclonal antibody that has transformed the landscape of treatment both for transplant-eligible and -ineligible patients with newly diagnosed multiple myeloma. Addressing important ongoing questions, such as when to de-escalate therapy, will be an important step forward in delivering patient-centred care for those with newly diagnosed multiple myeloma.

Immunotherapy is revolutionizing the treatment of many cancers and hepatocellular carcinoma (HCC) is no exception. This Review describes the heterogeneous immune microenvironments of HCC as well as their links with the various aetiologies underlying this malignancy and with response or resistance to immunotherapies. In addition, the authors provide an overview of the current landscape of clinical trials evaluating immunotherapies across all stages of HCC.

In the past few years, advances in omics technologies have led to a better understanding of the heterogeneity of triple-negative breast cancers (TNBCs) and their microenvironment, supporting a view of this breast cancer subtype as an ecosystem that encompasses the intrinsic and extrinsic features of cancer cells. The authors of this Review describe the current and upcoming therapeutic landscape of TNBC and discuss how an integrated view of the TNBC ecosystem can provide improved opportunities for tailoring treatment.

Efforts are being made to incorporate immune-checkpoint inhibitors into therapy for early stage non-small-cell lung cancer. The IMpower010 trial of adjuvant atezolizumab has recently become the first study to demonstrate that this strategy can improve disease-free survival in a subset of patients. This trial opens a new area of research in the quest for the optimal perioperative strategy to increase overall survival.