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  • Chromosomal instability (CIN) is a dynamic phenotype characterized by changes in chromosome number and structure and is a hallmark of clinically aggressive malignancies. Nonetheless, the ability of cancer cells to tolerate CIN creates several potential therapeutic vulnerabilities. In this Review, the authors describe the development of CIN and how this phenotype promotes carcinogenesis and tumour progression as well as describing the various attempts to develop targeted therapies based on the specific vulnerabilities of these tumours.

    • Duaa H. Al-Rawi
    • Emanuele Lettera
    • Samuel F. Bakhoum
    Review Article
  • The NETTER-2 trial provides the first phase III evidence that 177Lu-dotatate is active as first-line therapy in patients with gastroenteropancreatic neuroendocrine tumours with a Ki-67 proliferative index of 10–55%. This approach is an important addition to the first-line therapeutic armamentarium, although treatment selection based on patient-specific and tumour-specific characteristics remains appropriate.

    • Jonathan Strosberg
    • Mauro Cives
    News & Views
  • Traditionally, patients with small-cell lung cancer (SCLC), a malignancy with a dismal prognosis, have had limited treatment options. Over the past few years, advances in the molecular characterization of SCLC have revealed novel therapeutic targets. The authors of this Review summarize these findings and discuss emerging opportunities and challenges for their translation into new treatment approaches.

    • Triparna Sen
    • Nobuyuki Takahashi
    • Abdul Rafeh Naqash
    Review Article
  • Novel immunotherapeutic strategies based on targeting specific tumour-associated antigens with antibody–drug conjugates (ADCs), chimeric antigen receptor (CAR) T cells and bispecific T cell engagers (BTEs) are revolutionizing the treatment of multiple myeloma. In this Review, the authors describe the clinical experience to date with ADCs, CAR T cells and BTEs targeting B cell maturation antigen, G protein-coupled receptor family C group 5 member D and Fc receptor-like protein 5. In addition, they discuss the mechanisms of resistance to such therapies, and potential strategies by which resistance could be overcome to improve patient outcomes.

    • Paola Neri
    • Noémie Leblay
    • Kenneth C. Anderson
    Review Article
  • Artificial intelligence (AI) has the potential to dramatically change several aspects of oncology including diagnosis, early detection and treatment-related decision making. However, many of the underlying algorithms have been or are being trained on datasets that do not necessarily reflect the diversity of the target population. For this, and other reasons, many AI tools might not be suitable for application in less economically developed countries and/or in patients of certain ethnicities. In this Perspective, the authors discuss possible sources of inequity in AI development, and how to ensure the development and implementation of equitable AI tools for use in patients with cancer.

    • Vidya Sankar Viswanathan
    • Vani Parmar
    • Anant Madabhushi
    Perspective
  • Increasing evidence indicates that intratumoural bacteria can have crucial roles in both the pathogenesis and treatment of cancer. In this Review, the authors discuss the characteristics of intratumoural bacteria and the emerging understanding of their tumour-promoting and antitumour activities. They also describe a range of innovative strategies that are being used to engineer bacteria for use in the treatment of cancer and summarize clinical trials of various bacteria-mediated cancer immunotherapies.

    • Seong-Young Kwon
    • Hien Thi-Thu Ngo
    • Jung-Joon Min
    Review Article
  • Following the introduction of blinatumomab in 2014, the past 4 years have seen the approval of a further ten bispecific antibodies, reflecting substantial research effort and clinical interest in these agents. In this Review, the authors describe the developments leading to the approval of these novel agents and highlight important future research directions, including clinical optimization as well as innovative antibody engineering approaches.

    • Maria-Elisabeth Goebeler
    • Gernot Stuhler
    • Ralf Bargou
    Review Article
  • De-escalation of treatment for HER2+ breast cancer is a priority, given the increase in cure rates owing in part to improved HER2-targeted therapies. In this regard, the neoadjuvant approach provides the ideal platform to test less-intensive treatment regimens. Here we highlight a study that demonstrated the role of the metabolic response after dual HER2 blockade as a method of selecting patients who are most likely to benefit from chemotherapy-free neoadjuvant therapy.

    • Maria Vittoria Dieci
    • Valentina Guarneri
    News & Views
  • The majority of patients with cancers of unknown primary have unfavourable outcomes when they receive empirical chemotherapy. The shift towards using precision medicine-based treatment strategies involves two options: tissue-agnostic or site-specific approaches. Here, we reflect on how cytology-based deep learning tools can be leveraged in these approaches.

    • Elie Rassy
    • Nicholas Pavlidis
    News & Views