Volume 20 Issue 1, January 2023
News & Views
BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC
A high tumour mutational burden (≥10 mutations per megabase) is a companion biomarker in the histology-agnostic approval of pembrolizumab for treatment-refractory advanced-stage solid tumours, and continues to be an exploratory predictive biomarker for immune-checkpoint inhibitors in non-small-cell lung cancer. Herein, we discuss recent results from the first phase III trial evaluating blood-based tumour mutational burden in patients with treatment-naive advanced-stage non-small-cell lung cancer.
Clash of the titans: axi-cel versus tisa-cel for advanced-stage DLBCL
CAR T cell therapy has altered the natural history of relapsed and/or refractory diffuse large B cell lymphoma (DLBCL). However, the availability of multiple products has created provider uncertainty regarding treatment selection and the need to balance toxicity and efficacy. In a retrospective analysis, the authors suggest that axicabtagene ciloleucel might be superior to tisagenlecleucel. However, several questions remain unresolved.
Barriers in access to oncology drugs — a global crisis
In the past decade, oncologists worldwide have seen unprecedented advances in drug development and approvals but have also become increasingly cognizant of the rising costs of and increasing inequities in access to these therapies. These trends have resulted in the current problematic situation in which dramatic disparities in outcomes exist among patients with cancer worldwide owing, in part, to the lack of access to drugs that provide clinically meaningful benefits. In this Viewpoint, we have asked six oncologists working in different countries to describe how they perceive this issue in their region and propose potential solutions.
Neuroendocrine neoplasms of the lung and gastrointestinal system: convergent biology and a path to better therapies
Neuroendocrine neoplasms (NENs), which can develop in almost any organ and range from indolent neuroendocrine tumours (NETs) to rapidly progressive and fatal neuroendocrine carcinomas (NECs), have historically been approached in a siloed manner according to their specific tissue of origin. However, NETs and NECs across different sites of origin often share genomic and phenotypic characteristics. In this Review, the authors discuss both the clinical and biological commonalities as well as key organ-specific differences of NENs, with a focus on those of the gastrointestinal system and lung. Moreover, they advocate for a cross-cutting, tissue-agnostic approach to drug development for these rare tumours that might enable advances in one disease entity to accelerate research in others, ultimately improving patient care.
Targeting drugs to tumours using cell membrane-coated nanoparticles
Owing to several limitations, including elimination by the immune system and a lack of tumour specificity, systemically administered synthetic nanoparticles are used for a limited range of cancer indications. In this Review, the authors describe the potential of cellular nanoparticles (comprising a cell membrane coating around a synthetic core) to overcome these issues as well as their application in drug delivery, phototherapy and immunotherapy.
Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours
Chimeric antigen receptor (CAR) T cells are effective therapies for patients with relapsed and/or refractory B cell malignancies, partly owing to the ability to target B cell-specific antigens. However, CAR T cells targeting solid tumour antigens are likely to carry a higher risk of on-target, off-tumour toxicity (OTOT). Here, the authors summarize the available data on OTOT in the context of CAR T cells targeting solid tumour antigens and describe novel CAR T cell designs that might overcome such toxicities.