Featured
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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 |
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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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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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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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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Research Highlight |
Survival benefit with second-line combination in endometrial cancer
- Diana Romero
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Review Article |
Selecting the optimal immunotherapy regimen in driver-negative metastatic NSCLC
Immune-checkpoint inhibitors (ICIs) are now standard-of-care therapies for patients with advanced-stage non-small-cell lung cancer (NSCLC) without a targetable driver alteration. Various ICIs or combination regimens have been approved in this setting, relative to chemotherapy, although no prospective data are available comparing the various ICI-based approaches. Here, the authors provide guidance on selecting the optimal ICI-based therapy and highlight several future research directions that will probably further improve the outcomes of patients with advanced-stage NSCLC.
- Michael J. Grant
- , Roy S. Herbst
- & Sarah B. Goldberg
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News & Views |
CDK4/6 inhibitors for HR+HER2− early stage breast cancer — when to escalate treatment?
Opposing results of the monarchE and PALLAS trials investigating the role of adjuvant treatment with the CDK4/6 inhibitors abemaciclib and palbociclib, respectively, in patients with hormone receptor-positive, HER2-negative early stage breast cancer have recently been presented. Herein, potential reasons why these two drugs that have similar efficacy in the metastatic setting have produced disparate results in the adjuvant setting are discussed.
- Giuseppe Curigliano
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Abemaciclib crowned in monarchE
Biomarkers 101 — personalizing therapy for RCC