Reviews & Analysis

The protein tyrosine phosphatase (Ptp) family dephosphorylates target proteins and counters the activities of protein tyrosine kinases. Accumulating evidence indicates that some PTPs have an important role in the inhibition or control of growth, whereas some PTPs exert oncogenic functions. This Review discusses the relevance of PTPs to cancer biology and their potential as therapeutic targets.

Inherent difficulties with blocking many desirable targets using conventional approaches have prompted many to consider using RNA interference (RNAi) as a therapeutic approach. This Review explores current challenges to the development of synthetic RNAi-based therapies and considers new approaches to circumvent biological barriers.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease that often recurs, prompting the field cancerization hypothesis. This Review discusses the molecular pathology of HNSCC and how its heterogeneity can be used to classify the disease and provide a model of HNSCC development.

The Pim family of kinases actively collaborate with MYC in driving tumorigenesis. However, in several cancers the expression levels of PIMs can correlate with favourable prognostic outcome. This Review analyses the physiological and oncogenic activities of Pim kinases and their synergistic marriage with MYC, for better or for worse.

The survival of genetically abnormal carcinoma progenitor cells in ductal carcinomain situlesions could be driven by the hypoxic, nutrient-deprived microenvironment. Understanding the potential survival mechanisms, such as autophagy, could provide new strategies for arresting invasion at the pre-malignant stage.

Genetic analyses of the normal development of the nematodeCaenorhabditis elegans have revealed evolutionarily conserved mechanisms through which individual cells establish their fates, and how they make and execute the decision to survive or undergo programmed cell death. Mammalian counterparts of these pathways are co-opted by malignant cells, and studies in C.elegansare helping to identify new anticancer drugs.

The function of the deacetylase SIRT1 in cancer is complex and controversial. This article discusses the recent progress that has been made in mouse models to address the role of SIRT1 in tumour development.

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.

Adaptor (or scaffold) proteins form signalling platforms that regulate downstream signalling events. Evidence suggests that adaptors functioning downstream of integrins and receptor tyrosine kinases are deregulated in cancer and have important roles in mediating tumour cell survival, proliferation and motility.

Certain members of the Ras superfamily of small GTPases are commonly deregulated in human cancers, but how can we target them? This Review explores the association of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that regulate GTPases with cancer and discusses whether they can be effectively targeted therapeutically.

The polo-like kinases and aurora kinases have various roles in mitosis, and inhibitors of these kinases are being tested in clinical trials. Recent data have shown that extensive crosstalk exists between the polo-like kinase and aurora kinase pathways, which might affect the efficacy of these drugs. This Review discusses the biology of these kinases and how drugs that inhibit them might be used in the clinic.

The increasing number of cancer survivors has highlighted the problem of tumour dormancy, which can lead to relapse. Preclinical models and initial clinical trials are paving the way to address how best to treat long-term cancer survivors to minimize the risk of late cancer recurrence.

EGFRmutations define a subset of lung cancers associated with sensitivity to the kinase inhibitors gefitinib and erlotinib. However, primary and acquired resistance remains a major clinical problem. This article reviews recent advances towards biologically based rational treatment of this disease.

There are many similarities in tumour development between plants and animals, but fundamental differences prevent plants from developing cancer. In particular, cell division and proliferation are strictly regulated in plants, and plant tumours cannot metastasize owing to the rigid microenvironment surrounding plant cells (the cell wall). What can tumour development in plants tell us about cancer in animals?

This Review discusses the new data that have revealed surprising insights into the pathogenesis of acute promyelocytic leukaemia (APL) and the mechanism by which retinoic acid plus arsenic trioxide combination therapy targets the oncogenic fusion protein promyelocytic leukaemia (PML)–retinoic acid receptor-α (RARα), curing most cases of APL.

This Review describes the evidence linking the renin–angiotensin system (RAS) to cancer, through its roles in processes such as apoptosis, angiogenesis and tissue remodelling. Could RAS inhibitors currently used in the clinic be retooled to treat cancer?

Bacterial therapies have many advantages over standard cancer therapies — they specifically target tumours, induce controllable cytotoxicity and can be externally detected. This Innovation article proposes that synthetic biology can be applied to bacterial therapies and can tune their beneficial features, allowing the engineering of 'perfect' cancer therapies.

This article proposes a new model outlining the early steps in the development of serous ovarian cancer. This model suggests that homologous recombination repair deficiency initiates a cascade of molecular events that sculpt the evolution of high-grade serous ovarian cancer and dictate its response to therapy.

Kaposi's sarcoma (KS) is the most common cancer in HIV-infected untreated individuals. Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of KS. This Review discusses the insights into the remarkable mechanisms through which KSHV can induce KS that have been gained in the past 15 years.

Polycomb and trithorax group proteins have opposing effects on chromatin, and either repress or activate gene expression, respectively. Therefore, the dynamic interplay between these protein families has complex effects on epigenetic regulation and consequently tumour biology.