Reviews & Analysis

Five randomized trials have been conducted to prove that shorter duration of trastuzumab treatment (9 weeks or 6 months) can replace the standard duration (1 year). The results of PERSEPHONE, the most recent trial, suggest that the efficacy of a 6-month treatment is non-inferior to that of 1 year, although not for all patients. We discuss these results in the context of current treatment standards.

An urgent clinical need exists to improve the survival of patients with pancreatic cancer through biomarker-driven therapeutic strategies. Such approaches include the targeting of metastatic pancreatic cancer that harbours germline BRCA mutations with poly(ADP-ribose) polymerase inhibitors as maintenance therapy following platinum-based chemotherapy.

In the TITAN and ENZAMET trials, unprecedented overall survival outcomes were observed in patients with metastatic castration-sensitive prostate cancer receiving an agent targeting the androgen receptor in addition to androgen-deprivation therapy early in the course of their disease. Herein, I discuss both trials in the context of other studies in this disease setting.

The addition of the immune-checkpoint inhibitor nivolumab to first-line therapy with doxorubicin, vinblastine and dacarbazine seems feasible, with no signals of severe additional toxicities emerging. The high response rates and acceptable safety profile might make this combination an appealing alternative in the treatment of patients with high-risk disease.

With the development of novel targeted therapies for patients with colorectal cancer, comes a wealth of new, and increasingly complex information on biomarkers. In this Review, the authors describe this increased complexity, with a focus on interactions between more than one biomarker and the implications of these interactions for patient management.

In this Review, the authors present current insights into the genetic aetiology and pathogenesis of chronic lymphocytic leukaemia, highlighting the effect of recurrent lesions on progression, and discuss their clinical implications for management and development of novel therapeutic paradigmns.

Researchers from Google AI have presented results obtained using a deep learning model for the detection of lung cancer in screening CT images. The authors report a level of performance similar to, or better than, that of radiologists. However, these claims are currently too strong. The model is promising but needs further validation and could only be implemented if screening guidelines were adjusted to accept recommendations from black-box proprietary AI systems.

Despite their promise, immunotherapy–radiotherapy combinations could be limited by the patient-specific nature of radiation-induced immune responses. This Review discusses methods of assessing the immune response to radiotherapy and approaches to predict the synergy between immunotherapy and radiotherapy for personalized medicine.

The adoptive transfer of T cells expressing a chimeric antigen receptor (CAR) is an effective therapy for patients with relapsed or refractory CD19⁺ B cell malignancies, but can cause life-threatening toxicities. Herein we discuss a recent study suggesting that alterations to the design of anti-CD19 CARs can reduce cytokine release and the incidence of treatment-related complications.

The authors of this Review discuss treatments currently available for patients with head and neck squamous cell carcinomas (focusing in those of the oral cavity, oropharynx, hypopharynx and larynx). Advances in surgical and non-surgical approaches (mainly combinations of radiotherapy and chemotherapy) are discussed, including the first immunotherapeutic agents approved for these malignancies.

Neutrophils accumulate in the circulation of patients with cancer, and the neutrophil-to-lymphocyte ratio is a widely used biomarker. However, the effects of neutrophils on tumour development and progression, and the efficacy of therapies, remain relatively unknown. In this Review, the authors draw on data from animal models and patients with cancer to provide an overview of the effects of neutrophils in cancer.

Approximately 50% of patients with diffuse large B cell lymphoma (DLBCL) are cured with chemotherapy. However, patients with relapsed and/or refractory DLBCL have few other treatment options. In this Review, the authors describe emerging data on genetically targeted therapies for patients with DLBCL and how these might improve patient outcomes.

In a landmark analysis, investigators of the Multicentric Italian Lung Detection (MILD) trial have confirmed 10-year mortality reductions with lung cancer screening using low-dose helical CT (LDCT). These data complement the reduced lung cancer-specific mortality reported in the National Lung Screening Trial and reinforce the rationale for broad implementation of LDCT screening in high-risk populations.

In recent decades, cancer survival has improved dramatically, resulting in a growing population of cancer survivors with chronic health needs and disease risks. While large epidemiological studies are useful in tracking broad trends in health outcomes of cancer survivors, they lack the level of detail needed to inform the delivery of appropriate clinical care and optimal allocation of resources.

Identification of factors predicting recurrence of breast cancer is a long-standing goal, ranging from classical clinicopathological factors through to immunohistochemical assays of receptor levels and, more recently, the expression levels of several genes. A new paper now explores novel expression markers, especially for late recurrence of oestrogen receptor-positive breast cancer.

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.

The oligometastatic paradigm challenges the prevailing view of metastasis as a disseminated process and proposes the existence of a spectrum of biological virulence within metastatic lesions. The authors present evidence for this heterogeneity and discuss how it affects the staging and treatment of patients with metastatic cancer.

The therapeutic options currently available for patients with metastatic renal cell carcinoma (RCC) include immune-checkpoint inhibitors, novel targeted agents and combination strategies, and thus optimal patient selection and treatment sequencing are important. The authors review relevant aspects of the molecular biology of metastatic RCC, with an emphasis on biomarkers, and suggest tailored algorithms to individualize and guide treatment approaches

The authors of this Review propose a new model in which dynamic fluctuations of protein expression at the single-cell level and longitudinal reshaping of the cellular state at the cell-population level explain the process of therapeutic resistance development in patients with melanoma.

The metabolic conditions in tumours can result in phenotypic reprogramming of non-tumour cells, including immune cells, in the tumour microenvironment. This Review provides an overview of the pathways of cancer metabolism that intersect with immunometabolism, typically resulting in immunosuppression, with a focus on how these metabolic pathways could be targeted in order to enhance anticancer immunity and immunotherapy.