Browse Articles

Immune-checkpoint inhibitors (ICIs) have improved lung cancer outcomes, although resistance to these agents presents a substantial challenge. This Review describes the progress made in developing the next generation of immunotherapies for non-small-cell and small cell lung cancers, including novel immune-checkpoint modulators, immune cell engagers, adoptive cell therapies and therapeutic vaccines, as well as the mechanisms by which these agents might overcome resistance to the current generation of ICIs.

Liquid biopsy-based tests have demonstrated potential as a minimally invasive and broadly applicable approach to simultaneously screen individuals for multiple cancer types. In this Review, Wan, Sasieni and Rosenfeld discuss the promises and limitations of such multi-cancer early detection tests as well as future directions for this field.

Many women ≥75 years of age continue to undergo screening for breast cancer despite a lack of evidence supporting this practice. Evidence from the past 5 years suggests rising rates of breast cancer diagnosis in this age group without a corresponding increase in survival — either because the tumour itself is biologically indolent or because life-limiting comorbidities render a biologically aggressive tumour unlikely to further reduce life expectancy. Here, we review what we know, and what we do not know, about screening and overdiagnosis of breast cancer in women ≥75 years of age and build a case for active monitoring for selected screen-detected breast cancers in this population.

Patients with advanced-stage lung cancer might discontinue immune-checkpoint inhibitor (ICI) treatment for various reasons, including toxicities, disease progression or disease remission. Nonetheless, treatment options in this setting are often limited and some patients might derive benefit from re-administration of a previously received ICI. In this Review, the authors summarize the available data on ICI rechallenge, including the reasons for discontinuation and the feasibility of rechallenge in various clinical scenarios, and highlight important unaddressed research questions.

Despite being the second most lethal and the third most prevalent form of cancer, most cases of colorectal cancer (CRC) can be either detected at an early stage or prevented using screening colonoscopy with removal of precursor lesions. Nonetheless, universal colonoscopy is expensive and time consuming, and can be unpopular. Other less-invasive screening tests involving either faeces or more recently blood samples have the potential to improve overall CRC screening uptake and are an active area of research and development. In this Review, the authors describe the clinical utility of novel CRC screening methods such as multitarget stool DNA tests and blood cell-free DNA tests, including both the challenges and opportunities arising from their implementation.

Oncologists have crucial yet under-studied and often under-supported roles in promoting clinical trial referral and enrolment. Herein, we advocate for a systemic shift that acknowledges the operational barriers oncologists face and enhances structural support through streamlined workflows and behavioural science-informed strategies to facilitate their participation in clinical trial enrolment.

In pivotal trials testing daratumumab in patients with transplant-ineligible newly diagnosed multiple myeloma, inadequate crossover provisions have not only compromised the interpretation of survival data but also left fundamental questions about optimal treatment sequencing unanswered. Herein, we address the ethical implications of trial designs that fail to guarantee access to effective post-progression therapy for patients in the control arm, particularly in studies across regions in which standard-of-care treatment varies dramatically.

Despite advances in drug development, some patients with non-small-cell lung cancer (NSCLC) have suboptimal responses to treatment. The authors of this Review provide an overview of the complexity of the tumour microenvironment in NSCLC, including the influence of patient-related factors, such as ageing, sex and health disparities, on the cancer–TME crosstalk, and discuss how various therapeutic strategies interact with and are influenced by the TME in NSCLC.