Reviews & Analysis

In this Timeline article, Aasenet al. look back over 50 years of research linking gap junctions and connexins to cancer, highlighting the conditional nature of their role in cancer progression, future challenges and therapeutic strategies.

This Timeline article describes the discovery of the Epstein–Barr virus and summarizes the key advances in the field that have led to our current understanding of the role this virus plays in a number of different lymphoid and epithelial malignancies.

One interesting theme in the history of cancer research is the extent to which new biological insights and novel clinical applications have their origins in haematopoietic cancers. This Timeline article examines the roles that studies in leukaemia have had in this progress.

Research on the BCL-2-regulated apoptotic pathway has led to the development of small molecules called BH3-mimetics that bind to pro-survival BCL-2 proteins to induce apoptosis of malignant cells. This Timeline article describes the history of research on the BCL-2 family of proteins and their roles in cancer.

Research into the DNA damage response (DDR) was recently honoured by the Nobel Prize in Chemistry and the Lasker Award. In this Timeline article, the authors provide a historical perspective on our understanding of the role of the DDR in cancer.

Since the Philadelphia chromosome was discovered in 1960, studies over the past six decades have identified fusion genes, oncogenes that provide great diagnostic and therapeutic advantages because of their tumour-specific expression. This Timeline article revisits the spectrum of gene fusions in cancer and how the methods to identify them have evolved, and also discusses the implications of current, sequencing-based approaches for detection.

Lynch syndrome is caused by heterozygous mutations and epimutations in mismatch repair genes, which lead to specific pathologies, including increased risk of multiple types of cancer and microsatellite instability. Lynch syndrome has been pivotal to the history of understanding hereditary cancer-prone syndromes and continues to lead the way in our understanding of the risk and treatment of familial cancers.

The identification in 1993 of inherited mutations in the von Hippel–Lindau (VHL) gene in families with VHL disease was a seminal finding. This and subsequent discoveries have given the VHLtumour suppressor gene a central role in our understanding of the mechanisms of cellular oxygen sensing and in the pathobiology of clear-cell renal cell carcinoma.

In this Timeline, the authors discuss the identification of tumour antigens that are recognized by T lymphocytes and how these findings can be effectively and safely transferred to the clinic.

Myeloid-derived suppressor cells (MDSCs) remain steeped in mystery and controversy — how do we identify them? How are they recruited to the tumour microenvironment? How do they suppress antitumour immunity? This Timeline article discusses the discovery of MDSCs and what we know now — and need to know in the future — about the role of MDSCs in cancer biology.

More than 30 retroviral oncogenes have been discovered, and these predominantly function to control cellular signalling and replication. This Timeline article discusses a few of these oncogenes that are crucial in human cancer and that best illustrate the history of experimental and theoretical breakthroughs in this field.

This Timeline article focuses on the ERBB network of receptor tyrosine kinases, which exemplifies how a constant dialogue between basic and clinical cancer research can lead to the development of both novel drugs and strategies to overcome acquired resistance.

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.

Epigenetic alterations are leading candidates for the development of specific markers for cancer detection, diagnosis and prognosis, as well as new targets for cancer therapy. Which of the discoveries in the past 10 years are ready for advancement?

Will genomic and other systems level approaches help to overcome gaps in our understanding of metastasis?

It has been nearly 100 years since Francis Peyton Rous proved that sarcomatous chest tumours in Plymouth Rock hens could be caused by a virus. Since then, seven human viruses have been found to cause 10–15% of human cancers. This Timeline article explores the different techniques that helped in identifying these viruses, the common features they share and the different ways they evade innate immunity and cause cancer.

Proteomics approaches to characterize various aspects of cancer have increased as technology has improved. What are the challenges to cancer proteomics research and what could the future hold?

The four colony-stimulating factors (CSFs) regulate the generation and some functions of granulocytes and macrophages, and recombinant granulocyte-CSF and granulocyte–macrophage-CSF are used to treat patients with reduced white blood cell levels. How did we come to our understanding of the CSFs and what might the future opportunities be?

This Timeline article charts progress in mathematical modelling of cancer over the past 50 years, highlighting the different theoretical approaches that have been used to dissect the disease and the insights that have arisen.

This Timeline article looks back over 50 years of haematopoietic stem cell transplantation as a cancer therapy, highlighting the substantial advances that have been made to increase the specificity of this treatment for cancer cells, as well as improvements in availability, safety and patient outcomes.