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  • Advances in surgical technique and chemotherapy regimens have improved the survival outcomes of patients with pancreatic cancer, although these remain dismal relative to most other solid tumours. Attempts to further improve outcomes have led to increasing research interest in neoadjuvant therapy, which is beginning to improve the outcomes of certain subgroups of patients. In this Review, the authors provide an overview of the various neoadjuvant therapy approaches for patients with pancreatic cancer, including discussions of several promising future research directions

    • Christoph Springfeld
    • Cristina R. Ferrone
    • John Neoptolemos
    Review Article
  • Allele-specific inhibitors of KRASG12C are approved in non-small-cell lung cancer. Herein, we discuss recent results from the phase I/II KRYSTAL-1 trial of adagrasib alone and in combination with cetuximab in patients with KRASG12C-mutant metastatic colorectal cancer. The combination had promising efficacy and, if confirmed in later-phase trials, concomitant inhibition of EGFR and KRASG12C will present a new paradigm in precision oncology.

    • Federica Di Nicolantonio
    • Alberto Bardelli
    News & Views
  • Bladder cancer is among the ten most common cancers worldwide and therefore constitutes a substantial health-care burden. This Review summarizes the global trends in bladder cancer incidence and mortality, and describes the main risk factors associated with bladder cancer occurrence and outcomes. The implications, challenges and opportunities of these epidemiological trends for public health and clinical practice are also discussed.

    • Lisa M. C. van Hoogstraten
    • Alina Vrieling
    • Lambertus A. Kiemeney
    Review Article
  • Genomics-based precision medicine has improved the outcomes of patients with certain types of cancers, although most do not derive benefit. Here, the authors describe the development of functional patient-specific assays, including those based on organoids, spheroids and explants, and how clinical implementation of these models might extend the benefits of precision medicine to a much broader range of patients.

    • Allard W. J. van Renterghem
    • Joris van de Haar
    • Emile E. Voest
    Review Article
  • Neoadjuvant chemotherapy offers a pragmatic alternative to the difficulties associated with delivering timely adjuvant chemotherapy in rectal cancer. Enthusiasm for administering neoadjuvant therapy to all patients with locally advanced rectal cancer is based on data from several phase III trials. Data from the RAPIDO trial are a critical component of this evidence.

    • Robert Glynne-Jones
    • James Hollingshead
    News & Views
  • In 2022, the FDA approved numerous new drug and biologic agents, including targeted small molecules, immunotherapeutics, a gene therapy and a radiopharmaceutical. Several drug development challenges were also addressed, and key focus areas for the FDA Oncology Center of Excellence included ongoing monitoring of the Accelerated Approval programme and drug dose optimization.

    • Deepti Telaraja
    • Nicole Gormley
    • Richard Pazdur
  • Cachexia is a multi-organ syndrome characterized by substantial weight loss that affects a majority of patients with cancer and contributes to cancer-related mortality. The authors of this Review discuss the contribution of both the tumour macroenvironment and microenvironment to the inflammatory and metabolic processes involved in cancer-associated cachexia and provide an overview of the therapeutic strategies developed to manage this syndrome.

    • Josep M. Argilés
    • Francisco J. López-Soriano
    • Silvia Busquets
    Review Article
  • Lung cancers harbouring ‘rare’ alterations (defined as those with a prevalence of <5% of oncogene-driven lung cancers) can be detected in around a third of all oncogene-driven lung cancers and are diagnosed in thousands of patients each year. Advances in our understanding of tumour biology, diagnosis and the development of novel therapies are enabling increasing use of specific therapies targeting these alterations. In this Review, the authors provide an overview of the epidemiology, diagnosis, prognosis and treatment of patients with lung cancers harbouring these rare alterations. The importance of expedited drug approval pathways and cooperation between multiple stakeholders is also emphasized.

    • Guilherme Harada
    • Soo-Ryum Yang
    • Alexander Drilon
    Review Article
  • Plasma cell-free DNA analysis has emerged as a powerful liquid biopsy assay to assess circulating tumour DNA in response to cancer treatments. A new study shows that cell-free DNA can also inform on expansion kinetics and tumour-infiltration patterns in patients receiving chimeric antigen receptor T cells and, together with circulating tumour DNA, provides vivid prognostic insights into intratumoural dynamics.

    • Mark B. Leick
    • Marcela V. Maus
    News & Views
  • Protein degraders constitute a new class of agents that eliminate, rather than just inhibit, their target proteins. These novel agents have recently entered testing in oncology trials, with initial data providing clinical proof of concept for the mechanism of action as well as the antitumour activity of heterobifunctional protein degraders. In this Review, the authors outline the progress in the development of such protein degraders for the treatment of cancer and consider prospects and potential challenges for these agents.

    • Deborah Chirnomas
    • Keith R. Hornberger
    • Craig M. Crews
    Review Article
  • The development of modern immune-based therapies for multiple myeloma has expanded rapidly over the past several years, and GPRC5D has been identified as a viable immunotherapeutic target. Herein, we discuss data and provide future perspectives on GPRC5D-directed CAR T cells and bispecific antibodies for patients with relapsed and/or refractory multiple myeloma.

    • Karthik Nath
    • Bruno A. Costa
    • Sham Mailankody
  • Data obtained using omics technologies can offer important insights into various aspects of chimeric antigen receptor (CAR) T cell therapy. In this Review, the authors provide an overview of the multidimensional profiling technologies that have been applied in investigations of CAR T cell therapy. They then discuss the ways in which multi-omics data obtained through such analyses can be used to elucidate CAR targets, factors associated with response or resistance to therapy, and mechanisms underlying the associated toxicities, which could potentially be exploited to improve the efficacy and safety of CAR T cell therapies.

    • Jingwen Yang
    • Yamei Chen
    • Leng Han
    Review Article