Latest Reviews

  • Review Article |

    Technological advances have enabled the analysis of whole genomes, leading to the identification of causal factors that present new opportunities to prevent cancer. The authors of this Review discuss relevant findings in cancer genetics and genomics from the perspective of global cancer prevention and present a conceptual framework for the translation of such findings into clinical practice and evidence-based policies.

    • Ophira Ginsburg
    • , Patricia Ashton-Prolla
    • , Anna Cantor
    • , Daniela Mariosa
    •  & Paul Brennan
  • Review Article |

    Natural killer (NK) cells have an innate potential to kill cancerous cells and considerable effort is being focused on innovative approaches to leverage these cells for cancer therapy. Herein, the authors discuss the variety of NK cell-based therapies that are being developed for the treatment of diverse cancers and identify future avenues for NK cell therapy research.

    • Jacob A. Myers
    •  & Jeffrey S. Miller
  • Perspective |

    Genotyping is recommended for all patients with metastatic non-squamous non-small-cell lung cancers (NSCLC), both to enable patients to receive targeted therapies and to avoid therapies they are unlikely to benefit from. However, obtaining tumour biopsy material for genotyping is often challenging and is unfeasible in some patients, indicating the need to incorporate liquid biopsy approaches. In this Perspective, the authors provide guidance on how analysis of ctDNA from liquid biopsy samples in patients with metastatic NSCLC prior to first-line therapy has the potential to extend the benefits of genotyping to virtually all patients.

    • Charu Aggarwal
    • , Christian D. Rolfo
    • , Geoffrey R. Oxnard
    • , Jhanelle E. Gray
    • , Lynette M. Sholl
    •  & David R. Gandara
  • Review Article |

    Tumour budding is hypothesized to reflect the invasive and metastatic capacities of cancers and is accordingly associated with unfavourable patient outcomes. Herein, Lugli and colleagues describe the pathobiological characteristics of this phenomenon, including its associations with epithelial–mesenchymal transition and features of the tumour microenvironment, and review the evidence demonstrating the value of tumour budding as a prognostic biomarker across various solid cancers.

    • Alessandro Lugli
    • , Inti Zlobec
    • , Martin D. Berger
    • , Richard Kirsch
    •  & Iris D. Nagtegaal
  • Review Article |

    The number of adults aged ≥65 years with cancer is rapidly growing; these individuals continue to have worse outcomes than younger adults with cancer. The authors of this Review summarize the unique challenges of treating older adults with cancer owing to competing health and ageing-related conditions, and describe the current guidelines as well as investigational studies underway to improve the outcomes of these patients.

    • Sindhuja Kadambi
    • , Kah Poh Loh
    • , Richard Dunne
    • , Allison Magnuson
    • , Ronald Maggiore
    • , Jason Zittel
    • , Marie Flannery
    • , Julia Inglis
    • , Nikesha Gilmore
    • , Mostafa Mohamed
    • , Erika Ramsdale
    •  & Supriya Mohile
  • Perspective |

    The possible uses of artificial intelligence (AI) in radiation oncology are diverse and wide ranging. Herein, the authors discuss the potential applications of AI at each step of the radiation oncology workflow, which might improve the efficiency and overall quality of radiation therapy for patients with cancer. The authors also describe the associated challenges and provide their perspective on how AI platforms might change the roles of radiation oncology medical professionals.

    • Elizabeth Huynh
    • , Ahmed Hosny
    • , Christian Guthier
    • , Danielle S. Bitterman
    • , Steven F. Petit
    • , Daphne A. Haas-Kogan
    • , Benjamin Kann
    • , Hugo J. W. L. Aerts
    •  & Raymond H. Mak
  • Review Article |

    ROS1 fusions can be identified across a range of malignancies and confer a high level of sensitivity to ROS1 tyrosine kinase inhibitors. Herein, the authors discuss the non-malignant and malignant biology of ROS1, the diagnostic approaches to identifying ROS1 fusions and the current therapeutic concepts relating to ROS1 fusion-positive cancers, including the resistance mechanisms that have emerged with current ROS1 inhibitors.

    • Alexander Drilon
    • , Chelsea Jenkins
    • , Sudarshan Iyer
    • , Adam Schoenfeld
    • , Clare Keddy
    •  & Monika A. Davare
  • Review Article |

    The efficacy of chemotherapy in patients with cancer is now known to have an immunogenic component. Nonetheless, chemotherapy alone often fails to provide durable disease remission in most patients. The development of immune checkpoint inhibitors has created an opportunity to combine immunogenic chemotherapies with these agents in order to optimize patient outcomes. In this Review, the authors describe the mechanisms of synergy between chemotherapy and immune checkpoint inhibitors, summarize the available clinical data on these effects and highlight the most promising areas for future research.

    • Lorenzo Galluzzi
    • , Juliette Humeau
    • , Aitziber Buqué
    • , Laurence Zitvogel
    •  & Guido Kroemer
  • Review Article |

    TGFβ released by cancer cells and other cells in the tumour microenvironment enables cancer cell invasion and dissemination, stem cell properties and therapeutic resistance as well as generating an immunosuppressive environment. The authors of this Review introduce the mechanisms underlying TGFβ signalling in tumours and their microenvironment and discuss approaches to inhibit these signalling mechanisms, in particular in the context of cancer immunotherapy.

    • Rik Derynck
    • , Shannon J. Turley
    •  & Rosemary J. Akhurst
  • Review Article |

    Photodynamic and photothermal therapies hold promise in the local treatment of cancer although, arguably, their full potential has not yet been achieved. Herein, the authors review the current clinical progress of these phototherapies and discuss the bioengineering approaches that are being explored to overcome challenges and thereby improve such treatments.

    • Xingshu Li
    • , Jonathan F. Lovell
    • , Juyoung Yoon
    •  & Xiaoyuan Chen
  • Review Article |

    Most systemic cancer therapies are administered at doses at or close to the maximum tolerated dose until disease progression. However, this approach usually leads to treatment resistance and fails to take into account several potentially relevant evolutionary principles. In this Review, the authors describe how existing approaches to cancer therapy might be optimized by incorporating an understanding of evolutionary dynamics into cancer therapy.

    • Robert A. Gatenby
    •  & Joel S. Brown
  • Perspective |

    The availability and subsequent successes of immune-checkpoint inhibitors (ICIs) in patients with metastatic melanoma, and to a lesser extent in those with several other forms of cancer, have made long-term treatment-free remissions a realistic possibility for a subset of patients. In this Perspective, the authors describe available data on long-term remission from patients with melanoma and other solid tumours and provide early recommendations regarding the circumstances in which ICIs can be safely discontinued.

    • Caroline Robert
    • , Aurelien Marabelle
    • , Hugo Herrscher
    • , Caroline Caramella
    • , Pascal Rouby
    • , Karim Fizazi
    •  & Benjamin Besse
  • Consensus Statement
    | Open Access

    The analysis of ctDNA obtained from low-volume blood samples has the potential to transform the management of patients with colorectal cancer. Nevertheless, research priorities and minimum standards for sample collection and analysis in this area are currently missing. In this Position Paper, the NCI Colon and Rectal–Anal Task Forces provide a set of recommendations designed to address these challenges and accelerate the implementation of ctDNA in the management of patients with colorectal cancer.

    • Arvind Dasari
    • , Van K. Morris
    • , Carmen J. Allegra
    • , Chloe Atreya
    • , Al B. Benson III
    • , Patrick Boland
    • , Ki Chung
    • , Mehmet S. Copur
    • , Ryan B. Corcoran
    • , Dustin A. Deming
    • , Andrea Dwyer
    • , Maximilian Diehn
    • , Cathy Eng
    • , Thomas J. George
    • , Marc J. Gollub
    • , Rachel A. Goodwin
    • , Stanley R. Hamilton
    • , Jaclyn F. Hechtman
    • , Howard Hochster
    • , Theodore S. Hong
    • , Federico Innocenti
    • , Atif Iqbal
    • , Samuel A. Jacobs
    • , Hagen F. Kennecke
    • , James J. Lee
    • , Christopher H. Lieu
    • , Heinz-Josef Lenz
    • , O. Wolf Lindwasser
    • , Clara Montagut
    • , Bruno Odisio
    • , Fang-Shu Ou
    • , Laura Porter
    • , Kanwal Raghav
    • , Deborah Schrag
    • , Aaron J. Scott
    • , Qian Shi
    • , John H. Strickler
    • , Alan Venook
    • , Rona Yaeger
    • , Greg Yothers
    • , Y. Nancy You
    • , Jason A. Zell
    •  & Scott Kopetz
  • Publisher Correction |

    • Nora Pashayan
    • , Antonis C. Antoniou
    • , Urska Ivanus
    • , Laura J. Esserman
    • , Douglas F. Easton
    • , David French
    • , Gaby Sroczynski
    • , Per Hall
    • , Jack Cuzick
    • , D. Gareth Evans
    • , Jacques Simard
    • , Montserrat Garcia-Closas
    • , Rita Schmutzler
    • , Odette Wegwarth
    • , Paul Pharoah
    • , Sowmiya Moorthie
    • , Sandrine De Montgolfier
    • , Camille Baron
    • , Zdenko Herceg
    • , Clare Turnbull
    • , Corinne Balleyguier
    • , Paolo Giorgi Rossi
    • , Jelle Wesseling
    • , David Ritchie
    • , Marc Tischkowitz
    • , Mireille Broeders
    • , Dan Reisel
    • , Andres Metspalu
    • , Thomas Callender
    • , Harry de Koning
    • , Peter Devilee
    • , Suzette Delaloge
    • , Marjanka K. Schmidt
    •  & Martin Widschwendter
  • Review Article |

    Immune-checkpoint inhibition has transformed the treatment of patients with advanced-stage cancers. Nonetheless, the specific antigens targeted by T cells that are activated or reactivated by these agents remain largely unknown. In this Review, the authors describe the characterization and classification of tumour antigens including descriptions of the most appropriate detection methods, and discuss potential regulatory issues regarding the use of tumour antigen-based therapeutics.

    • Sebastian P. Haen
    • , Markus W. Löffler
    • , Hans-Georg Rammensee
    •  & Peter Brossart
  • Consensus Statement
    | Open Access

    Risk-adapted approaches to breast cancer prevention and screening could potentially be more effective than universal approaches, which have important limitations. In this Consensus Statement, representatives of the European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. They also present the ENVISION recommendations on priorities for future research in each of these areas with the aim of stimulating and guiding risk-adapted breast cancer prevention and screening programmes.

    • Nora Pashayan
    • , Antonis C. Antoniou
    • , Urska Ivanus
    • , Laura J. Esserman
    • , Douglas F. Easton
    • , David French
    • , Gaby Sroczynski
    • , Per Hall
    • , Jack Cuzick
    • , D. Gareth Evans
    • , Jacques Simard
    • , Montserrat Garcia-Closas
    • , Rita Schmutzler
    • , Odette Wegwarth
    • , Paul Pharoah
    • , Sowmiya Moorthie
    • , Sandrine De Montgolfier
    • , Camille Baron
    • , Zdenko Herceg
    • , Clare Turnbull
    • , Corinne Balleyguier
    • , Paolo Giorgi Rossi
    • , Jelle Wesseling
    • , David Ritchie
    • , Marc Tischkowitz
    • , Mireille Broeders
    • , Dan Reisel
    • , Andres Metspalu
    • , Thomas Callender
    • , Harry de Koning
    • , Peter Devilee
    • , Suzette Delaloge
    • , Marjanka K. Schmidt
    •  & Martin Widschwendter
  • Review Article |

    Therapies are being developed to treat cancers on the basis of specific molecular alterations and markers of immune phenotypes that transcend specific tumour histologies. The authors summarize the development and testing of approved histology-agnostic therapeutic agents, present data on other agents under development and discuss the challenges intrinsic to histology-agnostic drug development in oncology, including biological, regulatory, design and statistical considerations.

    • Roberto Carmagnani Pestana
    • , Shiraj Sen
    • , Brian P. Hobbs
    •  & David S. Hong
  • Review Article |

    Signalling induced by extracellular adenosine (eADO) can suppress antitumour immunity through multiple mechanisms. Herein, the authors review the pathophysiological functions of eADO in cancer and the related prognostic implications. They discuss the associated opportunities for eADO pathway-targeted immunotherapy, highlighting potential limitations and the scope for combination and biomarker-based strategies. The data emerging from oncology clinical trials of the diverse range of therapies that have been developed to target the eADO signalling pathway are also described.

    • Bertrand Allard
    • , David Allard
    • , Laurence Buisseret
    •  & John Stagg
  • Review Article |

    Therapies targeting MET-overexpressing cancers have limited efficacy. However, owing to advances in detection methods, therapies targeting MET-dependent tumours harbouring MET amplifications, activating mutations or fusions are emerging. In this review, the authors describe emerging data on this new class of targeted therapies.

    • Robin Guo
    • , Jia Luo
    • , Jason Chang
    • , Natasha Rekhtman
    • , Maria Arcila
    •  & Alexander Drilon
  • Perspective |

    Monitoring both cancer incidence and death rates is important for guiding health policy and the direction of future research. In this Perspective, the authors describe changes in cancer incidence and death rates in the USA, highlighting the effects of specific policies and research developments, and providing insight into unmet needs that should be addressed by future health policies.

    • Farhad Islami
    • , Rebecca L. Siegel
    •  & Ahmedin Jemal
  • Review Article |

    Important research efforts are being made to develop therapeutic strategies targeting the tumour microenvironment in pancreatic adenocarcinoma. The authors of this Review describe the apparent contradiction between preclinical studies and clinical outcomes observed to date, presenting more sophisticated strategies under active investigation.

    • Won Jin Ho
    • , Elizabeth M. Jaffee
    •  & Lei Zheng
  • Review Article |

    International treatment guidelines for chronic myeloid leukaemia incorporate recommendations for attempting discontinuation of treatment with tyrosine-kinase inhibitors (TKIs) with the aim of a treatment-free remission (TFR). The authors of this Review discuss how results of clinical studies of TFR can guide routine practice, address the development of predictors of outcome after TKI discontinuation and present strategies that warrant further consideration to enable more patients to enter TFR.

    • David M. Ross
    •  & Timothy P. Hughes
  • Review Article |

    Despite improvements in diagnostic strategies, cancer of unknown primary — metastatic cancer in patients in whom the primary tumour remains undetected — continues to account for around 1–2% of all cancers. In this Review, Rassy and Pavlidis discuss insights into the biology of CUP and shifts in the clinical management of this enigmatic disease entity in the era of precision medicine.

    • Elie Rassy
    •  & Nicholas Pavlidis
  • Review Article |

    Haematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for several haematological malignancies. Improvements in HSCT methodologies have considerably reduced treatment-related morbidity and mortality, thus broadening eligibility and placing increased emphasis on the prevention of disease relapse. In this Review, the authors discuss approaches to dissecting the biology of HSCT and exploiting the biological insights to enhance the graft-versus-tumour response, in particular with adoptive cell therapies and other immune-directed therapies, whilst minimizing graft-versus-host disease.

    • Bruce R. Blazar
    • , Geoffrey R. Hill
    •  & William J. Murphy
  • Review Article |

    Alternative splicing enables the regulated generation of multiple mRNA and protein products from a single gene. This Review outlines the splicing process and its alterations in cancer before highlighting related opportunities for the development of innovative therapeutic approaches.

    • Sophie C. Bonnal
    • , Irene López-Oreja
    •  & Juan Valcárcel
  • Review Article |

    Mutations in genes encoding subunits of the SWI/SNF chromatin-remodelling complexes occur in almost 25% of all cancers. Herein, Mittal and Roberts discuss the mechanisms by which these mutations might promote cancer and describe the associated vulnerabilities that provide opportunities for targeted therapy or immunotherapy with immune-checkpoint inhibitors.

    • Priya Mittal
    •  & Charles W. M. Roberts
  • Review Article |

    The treatment of immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors has mostly been based on adapting therapeutic approaches used in the management of primary autoimmune diseases. The authors of this Review provide an overview of the different cellular and soluble immune factors involved in the pathogenesis of irAEs in order to help clinicians deliver personalized immunopathologically guided treatment to manage these adverse events.

    • Khashayar Esfahani
    • , Arielle Elkrief
    • , Cassandra Calabrese
    • , Réjean Lapointe
    • , Marie Hudson
    • , Bertrand Routy
    • , Wilson H. Miller Jr
    •  & Leonard Calabrese
  • Review Article |

    The use of bispecific antibodies to engage cells of the immune system that are cytotoxic to cancer cells is a major focus of cancer immunotherapy, with approvals for the treatment of acute lymphoblastic leukaemia. Here, the authors review the clinical results obtained with bispecific antibodies to date. They also discuss the challenges associated with this therapeutic approach and the proposed solutions aimed at preventing or minimizing toxicities, countering immune escape and broadening the indications for these treatments.

    • Maria-Elisabeth Goebeler
    •  & Ralf C. Bargou
  • Review Article |

    The authors of this Review present the main pathways that regulate apoptosis as well as other signalling pathways that interact with them, highlighting actionable molecular targets for anticancer therapy. They also provide an overview of therapeutic agents exploiting apoptosis currently in clinical translation and known mechanisms of resistance to these agents.

    • Benedito A. Carneiro
    •  & Wafik S. El-Deiry
  • Review Article |

    Cancer cells, like non-malignant cells, are dependent on folate uptake for growth. However, cancer cells are much more reliant on folate receptors (FRs) and particularly FRα for folate uptake than non-malignant cells. In this Review, the authors describe the available data on the role of FRα as a biomarker and as a target of imaging probes, and of targeted therapies in patients with solid tumours.

    • Mariana Scaranti
    • , Elena Cojocaru
    • , Susana Banerjee
    •  & Udai Banerji
  • Review Article |

    Lineage plasticity is a source of intratumoural heterogeneity and enables tumour adaptation to an adverse tumour microenvironment, eventually leading to therapeutic resistance. The authors of this Review provide an overview of the impact of lineage plasticity on cancer progression and therapy resistance, with a focus on neuroendocrine transformation in lung and prostate tumours, and discuss emerging management strategies and open questions in the field.

    • Álvaro Quintanal-Villalonga
    • , Joseph M. Chan
    • , Helena A. Yu
    • , Dana Pe’er
    • , Charles L. Sawyers
    • , Triparna Sen
    •  & Charles M. Rudin
  • Perspective |

    Advances in imaging and biomarker discovery have led to a revolution in prostate cancer diagnosis, and nontargeted prostate biopsies should become obsolete. The authors of this Perspective article describe the current diagnostic pathway and discuss how advances in prebiopsy multiparametric MRI and the discovery of novel tumour markers should lead to a new diagnostic pathway.

    • Derek J. Lomas
    •  & Hashim U. Ahmed
  • Review Article |

    TRM cells have a role in peripheral immune surveillance in several organs. The presence of TRM cells in the immune infiltrate is also associated with improved outcomes in patients with several solid tumour types, and these cells might have a role in the response to immune checkpoint inhibitors. In this Review, the authors describe the available date on the role of TRM cells in patients with breast cancer

    • Ann Byrne
    • , Peter Savas
    • , Sneha Sant
    • , Ran Li
    • , Balaji Virassamy
    • , Stephen J. Luen
    • , Paul A. Beavis
    • , Laura K. Mackay
    • , Paul J. Neeson
    •  & Sherene Loi
  • Review Article |

    Brain metastases are a frequent manifestation of several common solid tumour types, including lung cancer, breast cancer and melanoma. Although the presence of brain-metastatic disease continues to be associated with poor outcomes, advances in surgery, radiotherapy and systemic therapies that can permeate the blood–brain barrier are beginning to improve patient outcomes. In this Review, the authors provide an overview of contemporary advances in the management of brain metastases over the past decade.

    • John H. Suh
    • , Rupesh Kotecha
    • , Samuel T. Chao
    • , Manmeet S. Ahluwalia
    • , Arjun Sahgal
    •  & Eric L. Chang
  • Perspective |

    Surgery remains a key pillar of cancer therapy, particular for those with curable, localized disease. The immediate perioperative period (days before and after surgery) is associated with various psychological and physiological stresses and associated factors, including inflammatory mediators, that might promote cancer progression and thus determine long-term outcomes. Herein, the authors present the hypothesis and supporting evidence that the use of certain types of immunotherapy, together with interventions to abrogate stress–inflammatory responses, in conjunction with surgery might improve the overall success of cancer treatment.

    • Pini Matzner
    • , Elad Sandbank
    • , Elad Neeman
    • , Oded Zmora
    • , Vijaya Gottumukkala
    •  & Shamgar Ben-Eliyahu
  • Review Article |

    Patients with small-cell lung cancer (SCLC) have historically received chemotherapy, typically with poor survival outcomes. In the past few years, the combination of immune-checkpoint inhibitors (ICIs) with chemotherapy has provided a more effective alternative to chemotherapy alone. Nonetheless, durations of survival are often short, and no robust biomarkers of response are available. In this Review, the authors provide a summary of the efficacy and safety of ICIs in patients with SCLC, and also highlight potential novel immunotherapeutic approaches that are currently in the early stages of investigation.

    • Wade T. Iams
    • , Jason Porter
    •  & Leora Horn
  • Perspective |

    An immunosuppressive tumour microenvironment is one of the main reasons why patients with solid tumours fail to respond to immune-checkpoint inhibition. In this Perspective, the authors describe the potential of nanomedicines to normalize the tumour microenvironment, thus overcoming this immunosuppressive barrier and enabling greater numbers of patients to respond to immune-checkpoint inhibition.

    • John D. Martin
    • , Horacio Cabral
    • , Triantafyllos Stylianopoulos
    •  & Rakesh K. Jain
  • Viewpoint |

    Regulatory approval of new cancer medicines can have important consequence for patients with advanced-stage and/or rare cancers who have exhausted all standard-of-care therapies. However, evidence that new medicines are safe and effective can also take time to accrue, and approval with a lack of evidence may cause unnecessary harm to patients. In this Viewpoint, we asked two leading oncologists involved in clinical drug development, an expert in regulatory science and prescription drug policy, and a prominent patient advocate, to provide their opinions on the current approach to cancer drug approvals.

    • Razelle Kurzrock
    • , Hagop M. Kantarjian
    • , Aaron S. Kesselheim
    •  & Ellen V. Sigal
  • Review Article |

    Chimeric antigen receptor (CAR) T cell therapy, the first approved therapeutic approach with a genetic engineering component, holds substantial promise in the treatment of a range of cancers but is nevertheless limited by various challenges, including toxicities, intrinsic and acquired resistance mechanisms, and manufacturing issues. In this Review, the authors describe the innovative approaches to the engineering of CAR T cell products that are providing solutions to these challenges and therefore have the potential to considerably improve the safety and effectiveness of treatment.

    • Sarwish Rafiq
    • , Christopher S. Hackett
    •  & Renier J. Brentjens
  • Review Article |

    HER2-targeted therapy has greatly improved the outcomes of patients with HER2-positive breast cancer, with a range of agents now approved or in late-stage clinical development. In the era of precision medicine, efforts are being made to further improve patient outcomes by personalizing HER2-targeted treatment regimens, primarily though escalation or de-escalation of therapy according to the disease biology. In this Review, the authors provide an overview of the current landscape of HER2-targeted therapy and discuss the evidence supporting such tailored therapeutic strategies.

    • Kristina Goutsouliak
    • , Jamunarani Veeraraghavan
    • , Vidyalakshmi Sethunath
    • , Carmine De Angelis
    • , C. Kent Osborne
    • , Mothaffar F. Rimawi
    •  & Rachel Schiff
  • Review Article |

    Cancer stem cells (CSCs) are implicated in cancer development, progression and resistance to treatment; therefore, the signalling pathways that mediate the CSC phenotype are attractive therapeutic targets. In this Review, the authors provide an update on the progress in targeting the Notch, WNT, Hedgehog and Hippo signalling pathways. Additionally, they discuss the interactions of CSCs with the immune system, the roles of CSC-related signalling pathways in immune cells and novel approaches to CSC-directed immunotherapy.

    • Joseph A. Clara
    • , Cecilia Monge
    • , Yingzi Yang
    •  & Naoko Takebe
  • Review Article |

    Systemic hormone therapies and chemotherapy are the cornerstones of treatment for patients with de novo metastatic prostate cancer, with a currently limited role for local treatments. Herein, the authors outline the pathobiological and immunological rationale for local cytoreductive treatment of the primary tumour and/or metastases in patients with this disease. They also review the preclinical and clinical evidence for the use of radical prostatectomy, prostate radiotherapy, minimally invasive ablative therapies, and metastasis-directed therapy (predominantly with stereotactic ablative radiotherapy) in this population.

    • Martin J. Connor
    • , Taimur T. Shah
    • , Gail Horan
    • , Charlotte L. Bevan
    • , Mathias Winkler
    •  & Hashim U. Ahmed
  • Review Article |

    Virtually all patients with resectable pancreatic ductal adenocarcinoma (PDAC) will have disease progression, which is generally associated with dismal outcomes. However, novel targeted therapies and immunotherapies, selected based on the genomic and/or clinical features of patients’ tumours are beginning to improve the outcomes in subsets of patients. In this Review, the authors describe progress in novel therapies for patients with PDAC.

    • Christopher Nevala-Plagemann
    • , Manuel Hidalgo
    •  & Ignacio Garrido-Laguna
  • Perspective |

    A systems biology-based approach incorporating multiscale, longitudinal measurements (from single-cell analyses to whole-body monitoring) would help to decipher the complexity of cancer and would facilitate the development of personalized therapies. The authors of this Perspective discuss how systems biology-based approaches can provide data for early detection of disease transitions, prediction of therapeutic responses and clinical outcomes, and for the design of personalized treatments.

    • James T. Yurkovich
    • , Qiang Tian
    • , Nathan D. Price
    •  & Leroy Hood
  • Review Article |

    Oncolytic viruses are beginning to enter clinical use in patients with cancer despite regulatory and practical considerations precluding the widespread use of such therapies. Here, the authors describe the potential of non-viral methods in achieving oncolytic effects and how these effects might prime the development of antitumour immune responses in patients with cancer.

    • Oliver Kepp
    • , Aurelien Marabelle
    • , Laurence Zitvogel
    •  & Guido Kroemer
  • Review Article |

    The use of epigenetic drugs (epi-drugs) as single agents according to a ‘one size fits all’ approach has generally resulted in disappointing therapeutic activity. In this Review, the mechanisms by which epi-drugs can modulate the sensitivity of cancer cells to other diverse forms of anticancer therapy are described, and completed and ongoing clinical trials relating to combination therapies incorporating epi-drugs are discussed. In addition, clinical trial designs and drug development strategies aimed at optimizing the development of such combinations are outlined.

    • Daphné Morel
    • , Daniel Jeffery
    • , Sandrine Aspeslagh
    • , Geneviève Almouzni
    •  & Sophie Postel-Vinay
  • Review Article |

    HER2-targeted therapies have dramatically improved the outcomes in women with HER2-positive breast cancer. Furthermore, genetic sequencing studies have revealed HER2 alterations in a range of other cancers, including gastric cancer, colorectal cancer and non-small-cell lung cancer. In this Review the authors describe the available data on HER2-targeted therapies beyond breast cancer.

    • Do-Youn Oh
    •  & Yung-Jue Bang
  • Review Article |

    Despite promising responses in a minority of patients with cancer, considerable scope remains to improve the efficacy of both immune-checkpoint inhibitors and epigenetic drugs, with one potential strategy involving the combination of these two types of treatment. Here, the authors describe the mechanisms underlying the synergy between immune-checkpoint inhibitors and epigenetic drugs and discuss the ongoing clinical development of such combinations.

    • Michael J. Topper
    • , Michelle Vaz
    • , Kristen A. Marrone
    • , Julie R. Brahmer
    •  & Stephen B. Baylin