Volume 19 Issue 12, December 2022
A high serum lactate dehydrogenase (LDH) level is generally associated with an inferior outcome in patients with most tumour types. LDH is also known to have immunosuppressive and/or tumour-promoting effects, suggesting a potentially broader role for this enzyme in clinical oncology. In this Review, the authors provide a holistic overview of the current role of LDH in both cancer biology and oncology, and highlight possible areas of future research interest, including the development of novel therapies targeting LDH.
Systemic therapies for early-stage disease have been tested in clinical trials for decades. The authors of this Review provide an overview of the evolution of (neo)adjuvant trials from the pre-genomic to the post-genomic era, focusing on design, end points and biomarkers that, together, could enable the delivery of more personalized treatment.
T cells are key effectors of immunotherapies that have revolutionized the treatment of cancer; however, chronic exposure to tumour-associated antigens can result in progressive loss of T cell effector functions and self-renewal capacity, a state termed ‘T cell exhaustion’ that is believed to limit the efficacy of immunotherapy. This Review synthesizes the new immunobiological insights that present a more nuanced view beyond T cell exhaustion being entirely undesirable and indicate that this hypofunctional state might be as much a reflection as it is the cause of poor tumour control. Hence, the authors describe how, in certain contexts, interruption of this programme could impair T cell persistence and discuss interventions to mitigate the development of T cell exhaustion that might ultimately improve clinical outcomes.
FLASH radiotherapy involves delivering ultra-high dose rates of radiation, which enables sustained tumour control with reduced toxicity to surrounding tissues. The authors of this Perspective describe the principles underlying FLASH radiotherapy, present the available evidence from preclinical studies testing this modality and discuss the challenges for its application in routine clinical practice.