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20th Anniversary

October 2021 marks the 20th anniversary of Nature Reviews Cancer. On this milestone birthday we both look back on the past 20 years of cancer research and look forward to the future. To celebrate, we present a Collection of cutting-edge articles, including our anniversary issue contents, and thought-provoking commentaries and viewpoints. We also delve into our archives as a reminder of where the journal started and all that has been achieved in cancer research since the journal’s launch.

Anniversary issue contents

Significant gaps in access to care have shifted the burden of cervical cancer disease to resource-poor countries in Africa, Asia and Latin America. The recent World Health Organization’s Call to Action to eliminate cervical cancer is a unique opportunity to galvanize change and remove barriers to prevention and care.

Comment | | Nature Reviews Cancer

A systematic approach to understanding the noncoding genome in cancer promises to improve cancer diagnosis and therapy. New technologies and bold therapeutic approaches are paving the way to truly envisage personalized cancer medicine in the future.

Comment | | Nature Reviews Cancer

Based on a virtual discussion during the American Association for Cancer Research (AACR) 2020 Annual Meeting, we asked several scientists actively working to improve representation of Black American populations in cancer research how they are addressing these issues.

Viewpoint | | Nature Reviews Cancer

The development of small-molecule degraders such as proteolysis-targeting chimeras (PROTACs) has made it possible to target oncoproteins previously considered undruggable. This Review discusses recent advances in the field, with a focus on opportunities and challenges for future development.

Review Article | | Nature Reviews Cancer

This Perspective discusses the main themes in cancer metabolism research that are currently under investigation in the context of in vivo tumour metabolism, specifically emphasizing emerging aspects and questions that remain unanswered.

Perspective | | Nature Reviews Cancer

Cutting edge

Clonal expansion in phenotypically normal or non-cancer tissues is commonly seen in association with ageing and/or in response to environmental insults and chronic inflammation, but does not necessarily indicate cancer development. This Review discusses recent findings on clonal expansion in these tissues and their biological significance in cancer development, ageing and inflammatory diseases.

Review Article | | Nature Reviews Cancer

The majority of cancers arise in individuals over the age of 60. This Review discusses how ageing tissues through changes in the extracellular matrix as well as in the functions of fibroblasts and immune cells can impact tumour initiation, progression and response to therapy.

Review Article | | Nature Reviews Cancer

This Perspective highlights the evidence from basic and translational research that genetic sex influences multiple factors that can contribute to cancer development and treatment responses, and suggests that including genetic sex considerations in treatments for patients with cancer will improve outcomes.

Perspective | | Nature Reviews Cancer

This Review discusses how fly tumours interact with the microenvironment and distant organs to influence disease progression and host physiology. The authors argue that the simplicity of flies and the ability to study lethality in this model provide an opportunity to address why patients ultimately die of cancer.

Review Article | | Nature Reviews Cancer

In vitro cancer models often fail to faithfully recapitulate the local tissue and organ microenvironment. Organs-on-chips can overcome this limitation and better mimic in vivo cancer phenotypes. This Review outlines the advances that have been made with this technology and explains the challenges that must be overcome to see its implementation into drug development pipelines and clinical cancer care.

Review Article | | Nature Reviews Cancer

After synthesis, all RNA molecules are subject to covalent modifications. This Review presents the evidence that RNA modification pathways are misregulated in cancer and suggests that they may be ideal targets for cancer therapy.

Review Article | | Nature Reviews Cancer

This Perspective discusses how therapeutic resistance is not only driven by genetic evolution but often involves non-genetic adaptive mechanisms that are intimately linked. Acknowledging these adaptive processes will enable the development of innovative strategies to monitor and counteract non-genetic therapy resistance as well as provide novel therapeutic avenues.

Perspective | | Nature Reviews Cancer

This Review provides a brief historical perspective of our understanding of the role of cancer genes before presenting the Integrative OncoGenomics (IntOGen) platform, a bioinformatics method of mutational driver identification, which is beginning to reveal the compendium of driver genes across many tumour types as well as alluding to their tumorigenic mechanisms.

Review Article | | Nature Reviews Cancer

Alterations in the extracellular matrix at the biochemical, biomechanical, architectural and topographical levels contribute to the development and progression of solid tumours. Our increased understanding of matrix biology is leading to the development of new approaches that co-target the matrix in cancer, including in metastasis.

Review Article | | Nature Reviews Cancer

This Perspective proposes operational definitions to define the hallmarks of cancer cell dormancy and, based on the latest evidence pertaining to the role of the microenvironment in regulating dormancy, presents key stages in the life cycle of a dormant cancer cell that could be targeted.

Perspective | | Nature Reviews Cancer

This Review discusses the role that nerves play in the initiation and progression of cancers, focusing on the evidence that tumours may reactivate nerve-mediated developmental and regenerative pathways to promote their own growth and survival.

Review Article | | Nature Reviews Cancer

This Consensus Statement highlights the importance of cancer-associated fibroblasts in cancer biology and progression, and issues a call to action for all cancer researchers to standardize assays and report metadata in studies of cancer-associated fibroblasts to advance our understanding of this important cell type in the tumour microenvironment.

Consensus Statement | Open Access | | Nature Reviews Cancer

This Review examines the tissue-specific metabolism and associated therapeutic vulnerabilities of mutant KRAS-driven tumours, providing a comparative discussion of intrinsic metabolism, co-occurring mutations and metabolic interactions in the microenvironment in colorectal, lung and pancreatic cancer.

Review Article | | Nature Reviews Cancer

This Review describes the metabolic rewiring that occurs in cancer cells transitioning through the metastatic cascade and discusses the evidence for metabolically distinct features of primary tumours and metastases.

Review Article | | Nature Reviews Cancer

This Review discusses our current understanding of adaptive and innate immune cell metabolism in the context of the tumour microenvironment, providing insight into the interaction of cancer cell metabolism and immune metabolism, as well as the potential for leveraging metabolic vulnerabilities to enhance the antitumour immune response.

Review Article | | Nature Reviews Cancer

An improved understanding of tumour immunology and therapy must assess the systemic immune landscape beyond the tumour microenvironment. This Review outlines peripheral immune cell reorganization in response to tumour growth and therapy, their contribution to immunotherapy responses and their potential as diagnostic or predictive biomarkers.

Review Article | | Nature Reviews Cancer

This Review broadly discusses therapeutic cancer vaccines, covering resistance mechanisms and strategies to overcome these, how to improve the antigen repertoire for vaccines and vaccine platforms, and approaches for enhancing immunotherapy efficacy.

Review Article | | Nature Reviews Cancer

This Review discusses the key role that natural killer (NK) cells play in driving an antitumour immune response throughout the progression of cancer from its initial development to its metastatic spread and eventual treatment, defined herein as the cancer–NK cell immunity cycle.

Review Article | | Nature Reviews Cancer

Innate immune checkpoints, including those regulating tumour detection and phagocytosis, have emerged as potential cancer immunotherapy targets. This Review discusses the role of phagocytosis checkpoints in cancer immune evasion, highlighting the preclinical and early clinical evidence supporting phagocytosis checkpoint blockade.

Review Article | | Nature Reviews Cancer

In addition to cancer cell-intrinsic effects, tumour growth can be regulated by cellular and molecular cues from the local tissue environment. This Review discusses how differences in cellular components and composition between tissue sites may influence the antitumour immune response, with potential implications for the design of therapeutic strategies.

Review Article | | Nature Reviews Cancer

This Review discusses recent work demonstrating that immune checkpoint inhibitor efficacy is affected by a combination of factors involving tumour genomics, host germline genetics, programmed cell death 1 ligand 1 (PDL1) levels and other features of the tumour microenvironment, as well as the gut microbiome.

Review Article | | Nature Reviews Cancer

Commentaries and Viewpoints

Opinions on where we should progress next with cancer research are diverse. In this article, four top cancer researchers from across the globe discuss their thoughts on the current state of cancer research and what progress might be expected in the next 10 years.

Viewpoint | | Nature Reviews Cancer

In this Viewpoint article, we asked four female scientists to describe their experiences of gender representation during their scientific careers and to identify the challenges and possible solutions to empowering women in cancer research and science more generally.

Viewpoint | | Nature Reviews Cancer

In this Viewpoint, we have asked recipients of the Nature Awards for Mentoring in Science about their views on good mentoring, and how mentorship can help to achieve a positive research culture and contribute to scientific discovery in cancer research.

Viewpoint | | Nature Reviews Cancer

There is evidence of a mounting mental health crisis among researchers, which may be exacerbated by the COVID-19 pandemic. This Comment article discusses what cancer researchers and institutions can do to promote good mental health and wellbeing within their research communities.

Comment | | Nature Reviews Cancer

The use of social media for the dissemination of published and unpublished scientific findings has exploded over the past few years. In this Comment article, Soragni and Maitra explain some of the ways in which Twitter can be used by academics to promote their science.

Comment | | Nature Reviews Cancer

Cancer genomics research in Africa is crucial to understanding the genetic architecture of cancer and tailoring cancer diagnoses and therapies to African populations. Creating this research enterprise in Africa has to be purposeful with a roadmap that incorporates individual scientist-, international collaborator-, university or institution-, and scientific organization-level factors.

Comment | | Nature Reviews Cancer

In this Viewpoint article, we asked four scientists working in the field of epithelial to mesenchymal transition (EMT) to provide their opinions on the role of this complicated phenomenon in cancer biology as well as the challenges of this fast-moving field and the directions it should take in the future.

Viewpoint | | Nature Reviews Cancer

In this Viewpoint article, we asked four scientists working on the cancer microbiome to provide their opinions on the current state of the field, where the research is heading and the challenges of implementing this field for clinical utility.

Viewpoint | | Nature Reviews Cancer

In this Viewpoint article, we asked four scientists working to target important, but so-called 'undruggable', proteins in cancer for their opinions on the most crucial advances, as well as the challenges and what the future holds for this important area of cancer research.

Viewpoint | | Nature Reviews Cancer

From the archive

This Review discusses mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and molecularly targeted therapies, which share many features. It is hoped that an improved understanding of the molecular basis of resistance will lead to rational drug combinations and predictive biomarkers.

Review Article | | Nature Reviews Cancer

Circulating tumour DNA (ctDNA) analysis has the potential to improve prognostication, molecular profiling and disease monitoring in patients with cancer. This Review summarizes recent advances, potential applications in cancer research and personalized oncology, and the introduction of ctDNA into clinical use.

Review Article | | Nature Reviews Cancer

MicroRNAs (miRNAs) are small, non-protein-coding RNAs that can repress the expression of important cancer-related genes. The mutation or mis-expression of several miRNAs is evident in human cancers, so will these novel RNAs prove useful in the diagnosis and treatment of cancer?

Review Article | | Nature Reviews Cancer

In this Opinion article, Schneideret al. outline tissue- and cell type-specific differences in tumorigenesis and the organization of oncogenic signalling pathways, and discuss the implications of our understanding of tissue context on molecularly targeted therapy and clinical trial design.

Opinion | | Nature Reviews Cancer

Neoplasms are microcosms of evolution. The evolution of neoplastic cells explains why we get cancer and why it has been so difficult to cure. Can evolutionary biology provide new insights into the clinical control of cancer?

Review Article | | Nature Reviews Cancer

Populations of tumour cells display remarkable phenotypic diversity as a result of both genetic and non-genetic influences. This Review discusses underlying causes of this intra-tumour phenotypic heterogeneity, and why this phenomenon may affect our ability to diagnose and effectively treat tumours.

Review Article | | Nature Reviews Cancer

The integrins regulate a diverse array of cellular functions that are crucial to the initiation, progression and metastasis of solid tumours. This Review discusses the exciting developments in targeting integrins, including the recent initiation of a Phase III trial for an integrin antagonist in patients with glioblastoma.

Review Article | | Nature Reviews Cancer

There is increasing debate about what is meant by the term 'cancer stem cell' (CSC) and the degree to which the concept of CSCs can provide insights into cancer biology and therapy. This Timeline article traces the historical milestones in normal and cancer stem cell biology as a backdrop to a discussion of how these fields have informed each other.

Timeline | | Nature Reviews Cancer

Fibroblasts are an important component of the tumour microenvironment. They become activated in tumours, as they do in healing wounds. Here, their roles in tumour initiation, progression and metastasis are reviewed.

Review Article | | Nature Reviews Cancer

This Review discusses the extrinsic regulation of angiogenesis by the tumour microenvironment, highlighting potential vulnerabilities that could be targeted to improve the applicability and reach of anti-angiogenic cancer therapies.

Review Article | | Nature Reviews Cancer

Metastatic dissemination and growth at distant sites are influenced by cells of the tumour microenvironment. What roles do these cells have in the underlying processes that determine metastatic growth?

Review Article | | Nature Reviews Cancer

Fundamental differences in the regulation of central metabolic pathways exist between tumours and normal tissue. This Review discusses how the Warburg effect is still applicable to our view of cancer metabolism and new advances in understanding beyond this hypothesis, including regulating anapleurosis and the redox balance.

Review Article | | Nature Reviews Cancer

Immune checkpoints refer to the plethora of inhibitory pathways that are crucial to maintaining self-tolerance. Tumour cells induce immune checkpoints to evade immunosurveillance. This Review discusses the progress in targeting immune checkpoints, the considerations for combinatorial therapy and the potential for additional immune-checkpoint targets.

Review Article | | Nature Reviews Cancer

This Review summarizes progress in applying nanotechnology to cancer treatment and discusses the challenges of clinical translation and opportunities to develop more effective nanotherapeutics through our increasing understanding of tumour biology and nano–bio interactions.

Review Article | | Nature Reviews Cancer