Lung cancer

There is encouraging news in the fight against the world’s most deadly form of cancer.

Refining immunotherapy, evaluating the benefits of screening, and other highlights from clinical trials and laboratory studies.

The disease remains highly lethal but advances in immunotherapy and targeted drugs bring a flicker of hope.

It is not a disease just for old men any more.

Metastasis to the brain is usually a swift death sentence but researchers are developing ways to make it less lethal.

Communities sharing particular types of the disease are helping steer research towards better therapies.

Technologies that count tumour cells in the blood promise to improve survival times.

Machine learning systems for early detection could save lives.

Targeted treatments for non-small cell lung cancer: recent progress and future challenges

Diehn and colleagues report that assaying circulating DNA in patients receiving chemoradiation therapy for non-small-cell lung cancer could identify the patients most likely to benefit from consolidation immunotherapy.

In a first-in-human phase I trial of patients with advanced lung cancer, infusions of autologous T cells edited to delete the PD-1 gene via CRISPR–Cas9 were well tolerated and did not lead to severe treatment-related adverse events.

Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

The first long-term study of how lung cancer evolves is revealing that therapies targeting multiple proteins in tumour cells could help to outpace the disease.

Tumours often become resistant to treatment, but how this occurs is poorly understood. An analysis of how the protein Rb affects tumour growth and the response to therapy might cast light on the problem.

Stewart et al. use circulating tumor cell-derived xenografts from patients with small-cell lung cancer to study tumor heterogeneity following the onset of therapeutic resistance.

Patients with small-cell lung cancer (SCLC) have historically received chemotherapy, typically with poor survival outcomes. In the past few years, the combination of immune-checkpoint inhibitors (ICIs) with chemotherapy has provided a more effective alternative to chemotherapy alone. Nonetheless, durations of survival are often short, and no robust biomarkers of response are available. In this Review, the authors provide a summary of the efficacy and safety of ICIs in patients with SCLC, and also highlight potential novel immunotherapeutic approaches that are currently in the early stages of investigation.

A multi-omics survey of progressive compared to regressive carcinoma in situ lesions provides a molecular map of early lung cancer development.

Co-occurring genomic alterations contribute to the heterogeneity of driver oncogene-defined non-small-cell lung cancer subgroups. This Review discusses the effects of co-mutations on the pathogenesis, biology, microenvironmental interactions and therapeutic vulnerabilities of non-small-cell lung cancer.

This Opinion, written by many leading experts in small cell lung cancer (SCLC) research, proposes a new model of SCLC subtypes defined by differential expression of four key transcription regulators. Such classification should help to focus and accelerate therapeutic research.

RNA sequencing data and tumour pathology observations of non-small-cell lung cancers indicate that the immune cell microenvironment exerts strong evolutionary selection pressures that shape the immune-evasion capacity of tumours.

Genotyping is recommended for all patients with metastatic non-squamous non-small-cell lung cancers (NSCLC), both to enable patients to receive targeted therapies and to avoid therapies they are unlikely to benefit from. However, obtaining tumour biopsy material for genotyping is often challenging and is unfeasible in some patients, indicating the need to incorporate liquid biopsy approaches. In this Perspective, the authors provide guidance on how analysis of ctDNA from liquid biopsy samples in patients with metastatic NSCLC prior to first-line therapy has the potential to extend the benefits of genotyping to virtually all patients.