Research Highlight |
Featured
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Research Highlight |
ALND can be safely omitted for patients with sentinel-node macrometastases
- David Killock
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Research Highlight |
Afami-cel provides a novel treatment option for rare sarcoma subtypes
- Peter Sidaway
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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 |
Pembrolizumab plus chemoradiotherapy effective in locally advanced cervical cancer
- Peter Sidaway
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Research Highlight |
Mirvetuximab soravtansine has activity in platinum-sensitive epithelial ovarian cancer
- Diana Romero
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News & Views |
Enhancing diagnostic precision in liver lesion analysis using a deep learning-based system: opportunities and challenges
A recent study reported the development and validation of the Liver Artificial Intelligence Diagnosis System (LiAIDS), a fully automated system that integrates deep learning for the diagnosis of liver lesions on the basis of contrast-enhanced CT scans and clinical information. This tool improved diagnostic precision, surpassed the accuracy of junior radiologists (and equalled that of senior radiologists) and streamlined patient triage. These advances underscore the potential of artificial intelligence to enhance hepatology care, although challenges to widespread clinical implementation remain.
- Jeong Min Lee
- & Jae Seok Bae
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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 |
FIRSTMAPPP prospectively charts the efficacy of sunitinib for phaeochromocytoma and paraganglioma
- David Killock
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Research Highlight |
Non-inferiority of simple versus radical hysterectomy in low-risk cervical cancer
- Diana Romero
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Review Article |
Dendritic cells as orchestrators of anticancer immunity and immunotherapy
Dendritic cells (DCs) are antigen-presenting cells that function at the interface between innate and adaptive immunity, thereby acting as key mediators of antitumour immune responses and immunotherapy efficacy. In this Review, the authors outline the emerging complexity of intratumoural DC states that is being revealed through single-cell analyses as well as the contributions of different DC subsets to anticancer immunity and the activity of immune-checkpoint inhibitors. The authors also discuss advances in the development of DC-based cancer therapies and considerations for their potential combination with other anticancer therapies.
- Ignacio Heras-Murillo
- , Irene Adán-Barrientos
- & David Sancho
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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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Review Article |
BRAF — a tumour-agnostic drug target with lineage-specific dependencies
Various BRAF alterations are found and function as oncogenic drivers across diverse cancer types. BRAF inhibitor-based therapy has improved outcomes for patients with cancers harbouring BRAFV600 mutations, although resistance develops in most, and the current inhibitors are not effective against other types of BRAF alterations. In this Review, the authors describe the mechanisms underlying oncogenic BRAF signalling, as well as pan-cancer and lineage-specific mechanisms of intrinsic, adaptive and acquired resistance to BRAF inhibitors. They also discuss novel RAF inhibitors and drug combinations designed to overcome these resistance mechanisms and/or expand the applicability of molecularly targeted therapy to a broader range of BRAF-mutant cancers.
- Aphrothiti J. Hanrahan
- , Ziyu Chen
- & David B. Solit
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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 |
Neoadjuvant chemoimmunotherapy is effective in locally advanced cervical cancer
- Diana Romero
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Research Highlight |
Tovorafenib effective against low-grade gliomas harbouring BRAF fusions
- Peter Sidaway
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Research Highlight |
Patients with uncommon EGFR mutations also benefit from first-line osimertinib
- Diana Romero
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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 |
Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy
Hepatocellular carcinoma (HCC) is among the most common causes of cancer-related death globally, and despite improvements in prevention and treatment strategies, continued increases in HCC incidence and mortality are predicted. Cirrhosis remains the major risk factor for HCC, although the underlying aetiology is shifting from virus-related to non-viral liver diseases. In this Review, the authors discuss the changing trends in HCC epidemiology and their implications for screening, prevention and therapy, including opportunities to further improve the management of patients with, or at high risk of, HCC.
- Amit G. Singal
- , Fasiha Kanwal
- & Josep M. Llovet
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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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Research Highlight |
Dabrafenib–trametinib is effective in paediatric high-grade glioma
- Diana Romero
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Review Article |
Biomarkers for immunotherapy of hepatocellular carcinoma
The availability of regimens containing one or more immune-checkpoint inhibitors (ICIs) has improved the outcomes in patients with advanced-stage hepatocellular carcinoma. However, clinical benefit from these regimens is difficult to predict, indicating the need for novel biomarkers. In this Review, the authors describe the available evidence on biomarkers to guide the use of ICIs in these patients and discuss promising future research directions.
- Tim F. Greten
- , Augusto Villanueva
- & Xin W. Wang
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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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Review Article |
TAM family kinases as therapeutic targets at the interface of cancer and immunity
The TAM (TYRO3, AXL and MERTK) family receptor tyrosine kinases (RTKs) have diverse cancer-promoting functions in malignant cells as well as immune cells and other cell types in the tumour microenvironment, presenting an attractive opportunity for both direct and immune-mediated therapeutic activity manifest through inhibition of a single target. Accordingly, a variety of agents designed to selectively target TAM RTKs are entering clinical testing. This Review provides an essential guide to the TAM RTKs for clinicians. The authors comprehensively review the various roles of TAM RTKs in cancer, the evidence supporting their potential as therapeutic targets, and the translational development of TAM-targeted agents as cancer treatments.
- Deborah DeRyckere
- , Justus M. Huelse
- & Douglas K. Graham
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Review Article |
Emerging therapeutics and evolving assessment criteria for intracranial metastases in patients with oncogene-driven non-small-cell lung cancer
Despite improved outcomes owing to advances in systemic targeted therapies, patients with brain metastases from oncogene-driven non-small-cell lung cancer continue to have a poor prognosis. This situation largely reflects the limited central nervous system (CNS) penetrance of most targeted therapies, a limitation that is beginning to be addressed with the development of later-generation agents. In this Review, the authors describe the CNS activity of targeted therapies for patients with oncogene-driven non-small-cell lung cancers, including discussions of novel agents with improved CNS penetrance and the potential of intrathecal administration for patients with leptomeningeal disease.
- Kelsey Pan
- , Kyle Concannon
- & Xiuning Le
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Research Highlight |
First-line pembrolizumab plus lenvatinib is effective in non-clear-cell RCC
- Diana Romero
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Research Highlight |
BRAF plus MEK inhibition effective in papillary craniopharyngioma
- Peter Sidaway
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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 |
Optimizing the safety of antibody–drug conjugates for patients with solid tumours
Advances in technology have enabled the development of several novel antibody–drug conjugates (ADCs) with encouraging clinical activity in patients with advanced-stage solid tumours. Indications for these therapies are expanding rapidly to earlier lines of therapy. Nonetheless, the toxicities of these various agents are not trivial and can be fatal, even in patients with early stage disease. In this Review, the authors summarize the toxicities of ADCs in patients with solid tumours both as monotherapies and in combination with other agents and discuss various ongoing research efforts attempting to optimize the therapeutic index of these agents.
- Paolo Tarantino
- , Biagio Ricciuti
- & Sara M. Tolaney
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Review Article |
Emerging evidence for adapting radiotherapy to immunotherapy
Radiotherapy has several key attributes that make it an attractive combination partner for immunotherapy; however, numerous clinical trials investigating the combination of these two treatment modalities have failed to demonstrate clear improvements in patient outcomes. In this Review, Galluzzi and colleagues discuss the evidence indicating that radiotherapy administered according to standard schedules and target volumes might impair immune fitness and, therefore, propose that adaptation of the radiotherapy regimens to immunotherapy (and not vice versa) might synergistically enhance the antitumour immune response to achieve meaningful clinical benefits.
- Lorenzo Galluzzi
- , Molykutty J. Aryankalayil
- & Silvia C. Formenti
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