Articles in 2019

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.

The negative results of the ANNOUNCE trial, resulting in withdrawal of olaratumab from the market, illustrate the difficulties in balancing access to novel therapies with the need for proven benefit.

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.