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  • Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of various haematological malignancies but is associated with characteristic toxicities as well as less well-defined adverse effects, many of which can be severe and potentially fatal. The increasing clinical experience with CAR T cell products has resulted in better recognition and management of these toxicities using a range of pharmacotherapies, although this is an area of continued evolution and refinement. In this Review, Brudno and Kochenderfer discuss the current understanding and clinical management of CAR T cell-associated toxicities.

    • Jennifer N. Brudno
    • James N. Kochenderfer
    Review Article
  • Lessons from the prevention of cervical cancer, the first cancer type deemed amenable to elimination, can provide information on strategies to manage other cancers. Infection with human papillomavirus (HPV) causes virtually all cervical cancers and an important proportion of other cancer types. The authors of this Review discuss the epidemiology of HPV-associated cancers and the potential for their elimination, focusing on the cofactors that could have the greatest effect on prevention efforts and health equity.

    • Talía Malagón
    • Eduardo L. Franco
    • Salvatore Vaccarella
    Review Article
  • Following their successful implementation in the COVID-19 pandemic, the technology behind mRNA vaccines is now being applied to cancer. In this Review, the authors described the several decades of development of mRNA vaccines for patients with cancer, including initial developments in this area involving cell-based vaccines as well as more recent developments with nanoparticle-encapsulated vaccines, which are beginning to show promising clinical activity.

    • Elias J. Sayour
    • David Boczkowski
    • Smita K. Nair
    Review Article
  • The question of whether chimeric antigen receptor (CAR) T cell therapies should be used in earlier lines (after 1–2 prior lines of therapy) in patients with relapsed and/or refractory multiple myeloma remains unanswered. Herein, I argue that the use of surrogate end points that lack a robust correlation with overall survival, as well as suboptimal control arms and use of post-progression therapies, limit the ability to make definitive conclusions on the basis of the available data.

    • Vinay Prasad
  • Expansion of the utilizable spectrum of light from the visible region to the near-infrared (NIR) window has greatly facilitated the clinical application of optical technologies for cancer imaging and phototherapy. However, use of light in the first NIR region (NIR-I) has important limitations, some of which might be overcome with emerging technologies utilizing NIR-II light. In this Review, the authors describe the current clinical experience with NIR-II-based cancer imaging and phototherapy, and discuss emerging NIR-II-based approaches that might further enhance patient outcomes. They also highlight challenges that will need to be addressed to translate NIR-II-based modalities from bench to bedside.

    • Zeyu Zhang
    • Yang Du
    • Jie Tian
    Review Article
  • The FDA has approved nanoliposomal irinotecan, 5-fluorouracil, leucovorin and oxaliplatin (NALIRIFOX) for patients with metastatic pancreatic adenocarcinoma on the basis of results from the NAPOLI 3 trial, in which this four-drug regimen improved overall survival relative to a doublet regimen. Here we discuss how, in the context of prior results from the PRODIGE 4 trial testing 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (modified FOLFIRINOX), NALIRIFOX does not seem to raise the bar, but rather exposes patients and health-care systems to financial toxicities.

    • Christopher Nevala-Plagemann
    • Ignacio Garrido-Laguna
    News & Views
  • Certain subsets of patients with multiple myeloma or its precursor conditions are overtreated with current approaches to therapy. Herein, we highlight several key areas where we believe de-escalation of treatment is needed. Dedicated trials to assess these de-escalation approaches and urgent changes to current clinical practices are needed.

    • Ghulam Rehman Mohyuddin
    • Aaron M. Goodman
  • By combining multiple MRI sequences, each providing different but complementary information about the tumour microenvironment (TME), multiparametric MRI (mpMRI) enables non-invasive assessment of the heterogeneous features of the TME components. The authors of this Review describe the role of mpMRI in the non-invasive characterization of the TME, presenting examples of its utility in cancer detection, staging and assessment of response to therapy, and considering future applications for personalized integrated diagnostics.

    • Emily Hoffmann
    • Max Masthoff
    • Moritz Wildgruber
    Review Article
  • T cell infiltration in the tumour microenvironment (TME) is a prerequisite for sustained antitumour immune responses. However, identifying predictive biomarkers that quantify T cell infiltration and the presence of proinflammatory TMEs associated with immune-checkpoint inhibitor (ICI) response for clinical implementation has proved challenging. Here, we highlight a study that validates a T cell-to-stroma enrichment score generated from RNA sequencing data as a novel biomarker for ICI response in patients with urothelial carcinoma.

    • David H. Aggen
    • Jonathan E. Rosenberg
    News & Views
  • The benefit of combining antiangiogenic agents with immune-checkpoint inhibitors has been demonstrated in pivotal phase III trials across different cancer types, some with practice-changing results; however, other phase III trials have had negative results. The authors of this Perspective discuss the variable outcomes of these trials, considering factors that account for these differences and suggesting future initiatives for improving the outcomes in patients receiving these combinations.

    • Hung-Yang Kuo
    • Kabir A. Khan
    • Robert S. Kerbel
  • Nucleic acid-based therapies offer an alternative to traditional cancer treatment modalities, with promising data beginning to emerge. In this Review, the authors describe the design and development of nucleic acid-based therapies administered virally and non-virally, including discussions of the advantages and disadvantage of each approach, as well as the role of patient-specific factors such as the tumour microenvironment, and consider the most promising future research directions.

    • Sebastian G. Huayamares
    • David Loughrey
    • Eric J. Sorscher
    Review Article
  • Ovarian cancer, accounting for 4.7% of cancer deaths in women in 2020, remains highly prevalent globally. Nonetheless, owing to changes in environmental exposures, the approach to preventive measures and disease classification, both incidence and mortality have been declining in economically developed countries since the early 2000s. Conversely, parts of Asia and eastern Europe have seen increases in the incidence of ovarian cancer over this period of time. In this Review, the authors summarize the epidemiology of ovarian cancer, including the roles of the various risk factors and the potential for prevention.

    • Penelope M. Webb
    • Susan J. Jordan
    Review Article