Research Highlight |
Featured
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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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Review Article |
Early stage gastric adenocarcinoma: clinical and molecular landscapes
Long-term survival rates of patients with gastric cancer remain low, particularly in Western countries. This lack of progress, among other aspects, is likely to reflect a focus on empirical approaches that fail to account for the heterogeneity of gastric cancers. In this Review, the authors summarize the available evidence on the management of patients with early stage gastric cancers, with an emphasis on understanding the underlying biology in order to improve the outcomes in patients with these historically difficult-to-treat tumours.
- Yuki Hirata
- , Ayesha Noorani
- & Jaffer A. Ajani
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Research Highlight |
Venetoclax–obinutuzumab combinations are effective in fit patients with CLL
- Diana Romero
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Review Article |
The roles and implications of RNA m6A modification in cancer
Dysregulation of N6-methyladenosine (m6A), the most prevalent internal modification in eukaryotic mRNA, is common in various cancer types. The authors of this Review provide an overview of the mechanisms of m6A-dependent RNA regulation, summarize current knowledge of their pathological effects and potential utility as biomarkers in cancer, and describe ongoing efforts to develop small-molecule inhibitors of oncogenic m6A modifiers.
- Xiaolan Deng
- , Ying Qing
- & Jianjun Chen
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Review Article |
Cholangiocarcinoma — novel biological insights and therapeutic strategies
Cholangiocarcinoma is a malignancy that continues to be associated with a dismal prognosis, and a better understanding of the disease biology is required to improve early detection and treatment strategies. In this Review, the authors describe key scientific and clinical advances made in this area over the past 5 years, encompassing novel insights into the tumour stroma and immune microenvironment, promising progress in developing liquid biopsy approaches for diagnosis and monitoring, clinical translation of molecularly targeted therapies, emerging immunotherapies and reassessment of the potential role of liver transplantation.
- Sumera I. Ilyas
- , Silvia Affo
- & Gregory J. Gores
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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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Review Article |
Understanding the activity of antibody–drug conjugates in primary and secondary brain tumours
Antibody–drug conjugates (ADCs) have demonstrated efficacy in patients with various cancers, although their antitumour activity in the central nervous system (CNS) might be limited by the blood–brain barrier. In this Review, the authors describe the available clinical data emphasizing the heterogeneous activity of ADCs against primary or secondary brain tumours and ongoing clinical trials in this area. In addition, they discuss physical, biological and molecular determinants of the CNS activity of ADCs, as well as potential strategies to improve delivery of these agents to brain tumours.
- Maximilian J. Mair
- , Rupert Bartsch
- & Matthias Preusser
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Review Article |
Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention
Globally, gastric cancer is a common and highly fatal cancer with two anatomical subtypes, non-cardia and cardia gastric cancer. Helicobacter pylori causes almost 90% of distal gastric cancers worldwide. The authors of this Review summarize the current epidemiology of gastric cancer and the evidence and implications of primary and secondary prevention efforts.
- Aaron P. Thrift
- , Theresa Nguyen Wenker
- & Hashem B. El-Serag
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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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Review Article |
Global trends in the epidemiology of bladder cancer: challenges for public health and clinical practice
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
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Review Article |
Functional precision oncology using patient-derived assays: bridging genotype and phenotype
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
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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 |
Rare molecular subtypes of lung cancer
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
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Review Article |
Cancer-associated cachexia — understanding the tumour macroenvironment and microenvironment to improve management
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
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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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Comment |
GPRC5D as a novel immunotherapeutic target in multiple myeloma
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
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Research Highlight |
Early MRD predicts disease recurrence and benefit from adjuvant chemotherapy in CRC
- David Killock
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Review Article |
The emerging roles of γδ T cells in cancer immunotherapy
γδ T cells are lymphocytes with properties of both typical αβ T cell and natural killer cells, notable tissue tropisms, and MHC-independent antitumour functions that make them attractive agents for cancer immunotherapy. In this Review, the authors provide an overview of human γδ T cell subsets, discuss the antitumour and pro-tumour activities of these cells and their prognostic value in patients with cancer, and describe the current landscape of γδ T cell-based immunotherapies.
- Sofia Mensurado
- , Rafael Blanco-Domínguez
- & Bruno Silva-Santos
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Review Article |
Thermal immuno-nanomedicine in cancer
Immunotherapies have dramatically improved the outcomes of a subset of patients with advanced-stage cancers. Nonetheless, most patients will not respond to these agents and adverse events can be severe. In this Review, the authors describe the potential to address these challenges by combining immunotherapies with currently available thermal therapies as well as by using thermal immuno-nanomedicines.
- Zhe Yang
- , Di Gao
- & Xingcai Zhang
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Review Article |
Advances in the clinical management of uveal melanoma
Although almost all patients with uveal melanoma have localized disease at diagnosis, and despite effective treatment of the primary tumour, metastatic recurrence is common and holds a dismal prognosis. Unlike its cutaneous counterpart, therapeutic advances for uveal melanoma have not been forthcoming, although the recent approval of the first systemic therapy for this disease has ushered in a new era of hope. This Review summarizes the biology of uveal melanoma and the management of primary disease, including molecular risk classification, adjuvant therapy and follow-up strategies. The discussion is then focused on the established and emerging regional and systemic treatments for metastatic uveal melanoma.
- Richard D. Carvajal
- , Joseph J. Sacco
- & Sophie Piperno-Neumann
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News & Views |
Perioperative immunotherapy for renal cell carcinoma: looking beyond the data
The first phase III trial to test perioperative immune-checkpoint inhibitor therapy for high-risk renal cell carcinoma yielded highly promising results, leading to regulatory approvals of adjuvant pembrolizumab. However, subsequent phase III trials, including the IMmotion010 trial of adjuvant atezolizumab, did not demonstrate similar benefits. Although molecular biomarkers are urgently needed to better delineate responder subgroups, the unique design of each trial might partially explain some of the patterns identified.
- Chris Labaki
- & Toni K. Choueiri
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Review Article |
Overcoming on-target, off-tumour toxicity of CAR T cell therapy for solid tumours
Chimeric antigen receptor (CAR) T cells are effective therapies for patients with relapsed and/or refractory B cell malignancies, partly owing to the ability to target B cell-specific antigens. However, CAR T cells targeting solid tumour antigens are likely to carry a higher risk of on-target, off-tumour toxicity (OTOT). Here, the authors summarize the available data on OTOT in the context of CAR T cells targeting solid tumour antigens and describe novel CAR T cell designs that might overcome such toxicities.
- Christian L. Flugel
- , Robbie G. Majzner
- & Mohamed Abou-el-Enein
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Review Article |
Targeting drugs to tumours using cell membrane-coated nanoparticles
Owing to several limitations, including elimination by the immune system and a lack of tumour specificity, systemically administered synthetic nanoparticles are used for a limited range of cancer indications. In this Review, the authors describe the potential of cellular nanoparticles (comprising a cell membrane coating around a synthetic core) to overcome these issues as well as their application in drug delivery, phototherapy and immunotherapy.
- Ronnie H. Fang
- , Weiwei Gao
- & Liangfang Zhang
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