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The need to address COVID-19 is placing huge demands on biomedical research and regulatory processes. Under pressure, it is essential to uphold high bioethical principles and rigorous standards for the development and approval of medicines.
Immunotherapy has changed the treatment paradigm for patients with cancer, but patient selection, response assessment and treatment duration require further refinement. A recent study reports that the kinetics of circulating tumor DNA reflect response and resistance to immunotherapy treatment across multiple cancer types and could be used to tailor treatment.
Locally injected lipid nanoparticles that deliver RNA to elicit danger signals and simultaneously contain RNA that encodes a membrane-anchored version of the cytokine IL-12 can induce immunogenic cell death in tumors. This multipronged platform induces anticancer immune responses to the injected lesion as well as to distant tumors and hence produces an abscopal effect.
The urea cycle enzyme argininosuccinate synthase 1 (ASS1) is upregulated in some cancer types. A study now shows that tumor cells with elevated urea cycle activity due to high ASS1 expression enhance gluconeogenesis, enabling a metabolic shift toward serine synthesis and causing purine synthesis addiction for growth and proliferation.
Zhang and Meyerson review exciting advances in methodologies, models and datasets to study noncoding alterations in cancer, new insights into their roles in disease and potential translational implications.
Siu and colleagues use a bespoke ctDNA assay and show predictive utility of longitudinal ctDNA analysis in a phase II clinical trial of patients receiving pembrolizumab that included multiple solid tumor types.
Irvine and colleagues present a lipid nanoparticle platform containing self-replicating interleukin-12 RNA, which showed therapeutic efficacy in vivo by promoting immunogenic cell death and priming CD8+ T cells.
Erez and colleagues demonstrate that increased expression of arginosuccinate synthase under glucose deprivation leads to gluconeogenesis and increased purine synthesis, which when targeted can enhance response to immune checkpoint blockade.
ARID1A/B loss causes oncogenic BAF complex redistribution. Zhu and colleagues show that concomitant ARID1A and ARID1B loss results in carcinogenesis and disruptive redistribution of residual cBAF subcomplexes, impairing pBAF function.