Featured
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News & Views |
Gaining ground in personalized breast cancer therapy: lesson learned from PHERGain
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
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Review Article |
Current understanding and management of CAR T cell-associated toxicities
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
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Research Highlight |
ALND can be safely omitted for patients with sentinel-node macrometastases
- David Killock
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News & Views |
Lighting the torch: intratumoural T cell-to-stroma enrichment score as a predictor of immunotherapy response in urothelial carcinoma
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
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Research Highlight |
IL-13Rα2-targeted CAR T cells show promise in patients with recurrent high-grade gliomas
- David Killock
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Review Article |
Targeting cuproplasia and cuproptosis in cancer
Copper is an essential trace element with inherent redox properties and fundamental roles in a diverse range of biological processes; therefore, maintaining copper homeostasis is crucial. In this Review, the authors discuss new insights into the mechanisms by which disrupted copper homeostasis contributes to tumour initiation and development, including the recently defined concepts of cuproplasia (copper-dependent cell growth and proliferation) and cuproptosis (a mitochondrial pathway of cell death triggered by excessive copper exposure). They also discuss potential strategies to exploit cuproplasia and cuproptosis for the treatment of cancer.
- Daolin Tang
- , Guido Kroemer
- & Rui Kang
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Research Highlight |
Non-inferiority of simple versus radical hysterectomy in low-risk cervical cancer
- Diana Romero
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Research Highlight |
Tabelecleucel is effective in EBV-positive lymphoproliferative disease
- Diana Romero
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Research Highlight |
Personalized neoantigen mRNA vaccine mitigates melanoma recurrence
- David Killock
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News & Views |
Combination strategies for advanced-stage urothelial carcinoma: a paradigm shift
Durable responses with first-line platinum-based chemotherapy for advanced-stage urothelial carcinoma are rare, and patient outcomes are poor. Recently, CheckMate 901 became the first phase III trial to establish a significant overall survival benefit from a combined chemoimmunotherapy approach in this disease setting. Herein, we discuss key findings from CheckMate 901 and their implications in the context of a rapidly evolving treatment landscape.
- Nimira Alimohamed
- & Srikala S. Sridhar
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Research Highlight |
PERSEUS triumphs — efficacy of daratumumab confirmed in transplant-eligible NDMM
- David Killock
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News & Views |
Pyrotinib in combination with first-line trastuzumab and docetaxel for patients with HER2-positive metastatic breast cancer: a new therapeutic option?
Recent results from the phase III PHILA trial demonstrate a benefit in terms of progression-free survival derived from the addition of pyrotinib to first-line chemotherapy plus trastuzumab in patients with metastatic HER2-positive breast cancer. Dual HER2 blockade with pyrotinib and trastuzumab is an effective therapeutic strategy but might increase the risk of gastrointestinal toxicity; therefore, the risk-to-benefit ratio should be carefully evaluated.
- Pier Paolo M. Berton Giachetti
- & Giuseppe Curigliano
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Research Highlight |
From CHRYSALIS to PAPILLON: the metamorphosis of amivantamab into frontline therapy for NSCLC
- David Killock
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Review Article |
Molecular tumour boards — current and future considerations for precision oncology
According to the precision oncology paradigm, cancer therapies are increasingly being matched to specific sensitizing alterations using a biomarker-directed approach. However, the criteria for determining the actionability of molecular alterations and selecting matched treatments evolve over time. Molecular tumour boards (MTBs) have emerged as means to capitalize on the collective knowledge of various experts to interpret molecular-profiling data and to eliminate subjectivity in treatment selection. This Review describes the components, processes and increasingly important role of MTBs in optimizing the implementation of precision oncology in both clinical trials and clinical practice, as well as current and future considerations for ensuring the sustainability of MTBs and expanding their outreach to underserved populations.
- Apostolia M. Tsimberidou
- , Michael Kahle
- & Funda Meric-Bernstam
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News & Views |
Harnessing potent therapies with care: enfortumab vedotin plus pembrolizumab for advanced-stage urothelial carcinoma
Following the recent FDA Accelerated Approval of enfortumab vedotin (EV) plus pembrolizumab for patients with advanced-stage urothelial carcinoma who are cisplatin-ineligible, herein we highlight key clinical outcomes with this combination based on results from Cohort K of the pivotal phase Ib/II EV-103 trial. We also discuss treatment sequencing, de-escalation strategies and toxicity management as EV–pembrolizumab becomes widely used in clinical practice.
- Pooja Ghatalia
- & Elizabeth R. Plimack
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Research Highlight |
First-line pembrolizumab plus lenvatinib is effective in non-clear-cell RCC
- Diana Romero
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News & Views |
A critical appraisal of the ATLAS trial of maintenance therapy for multiple myeloma: end points, censoring and equipoise
A recent report from the ATLAS trial comparing different maintenance strategies following haematopoeitic stem cell transplantation for multiple myeloma provides an opportunity to explore various themes of critical appraisal, including end points, the equipoise of trial design, and the part censoring can play in the validity of results.
- Ghulam Rehman Mohyuddin
- & Tomer Meirson
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Review Article |
Improving outcomes in patients with oesophageal cancer
Oesophageal cancer is one of the most common malignancies worldwide and is associated with considerable morbidity and mortality. In this Review, the authors highlight advances made across the disease continuum that have improved the management and outcomes of patients with oesophageal cancer. These advances include an increased understanding of the disease biology, improvements in screening, the development of minimally invasive endoscopic monitoring and management technologies, refinement of surgical techniques and perioperative management, and novel radiotherapy and systemic therapy approaches. Continual multidisciplinary efforts across all these aspects of care will further improve patient outcomes.
- Manish A. Shah
- , Nasser Altorki
- & Julian A. Abrams
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News & Views |
Combination immunomodulation for immune-checkpoint-inhibitor-associated myocarditis
Immune-checkpoint-inhibitor-associated myocarditis has a high fatality rate, warranting the development of more-effective treatment strategies. Herein, we discuss a recent report of a series of patients who were managed using a novel approach that involved personalized abatacept dosing, ruxolitinib and close respiratory monitoring, which was associated with low mortality.
- Douglas B. Johnson
- & Alexander M. Menzies
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Review Article |
Neoadjuvant therapy for pancreatic cancer
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
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Research Highlight |
Recurrent nasopharyngeal carcinoma: hyperfractionation of IMRT improves outcomes
- David Killock
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Research Highlight |
Sublobar resection is non-inferior to lobectomy in very early stage NSCLC
- Diana Romero
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Review Article |
Protein degraders enter the clinic — a new approach to cancer therapy
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
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Research Highlight |
Docetaxel-based CRT improves survival in cisplatin-ineligible patients
- David Killock
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Research Highlight |
Early MRD predicts disease recurrence and benefit from adjuvant chemotherapy in CRC
- David Killock
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News & Views |
BFAST but be smart: bTMB remains an exploratory biomarker in NSCLC
A high tumour mutational burden (≥10 mutations per megabase) is a companion biomarker in the histology-agnostic approval of pembrolizumab for treatment-refractory advanced-stage solid tumours, and continues to be an exploratory predictive biomarker for immune-checkpoint inhibitors in non-small-cell lung cancer. Herein, we discuss recent results from the first phase III trial evaluating blood-based tumour mutational burden in patients with treatment-naive advanced-stage non-small-cell lung cancer.
- So Yeon Kim
- & Roy S. Herbst
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