Reviews & Analysis

Of the two main urokinase plasminogen activator inhibitors, high tumour levels of the type 1 inhibitor promote tumour progression, whereas high levels of the type 2 inhibitor decrease tumour growth and metastasis. What might be the basis of this paradoxical action?

Using recent evidence from mouse models, this Review discusses whether p53-dependent senescence induced by dysfunctional telomeres is as potent as apoptosis in suppressing tumorigenesisin vivo.

Hypoxia and free radicals, such as reactive oxygen and nitrogen species, alter the activity of the transcription factor HIF1, which can regulate tumour cell survival and angiogenesis. Intratumoural heterogeneity of these factors significantly affects HIF1 and consequently the response to cytotoxic therapy.

Cell cycle progression is regulated by phosphorylation and protein degradation, which is mediated by ubiquitin ligases. This Review explores the relevance of two ubiquitin ligase specificity factors (F-box proteins) that are emerging as important players in tumour development.

CDC37 is oncogenic because it stabilizes the structures of mutated or overexpressed oncogenic kinases. Targeting this chaperone activity, on which many tumours depend, is therefore an attractive option for broad-based therapy.

Cancer stem cell content and the intrinsic radiosensitivity of cancer stem cells is thought to vary between tumours, thereby affecting their radiocurability. What do we know about cancer stem cells in radioresistance and how might this information be used?

Angiogenesis and lymphangiogenesis are regulated by integrins, which are cell surface receptors whose ligands are extracellular matrix proteins and immunoglobulin superfamily molecules. Here, the evidence implicating integrins as regulators of angiogenesis and lymphangiogenesis and the current state of therapeutic strategies to target them are discussed.

Recent advances in our understanding of intestinal crypt biology, including how mutations in stem cells become fixed and expand within the epithelium, has led to new theories on the origins of colonic adenomas and cancers.

One hundred years ago, Paul Ehrlich received the Nobel Prize for Physiology or Medicine. His idea of creating 'magic bullets' for use in the fight against human diseases has inspired generations of scientists to devise powerful molecular cancer therapeutics.

The Wnt signalling pathway has a crucial role in the development of all animal species, and mutations or deregulated expression of components of the Wnt pathway can result in cancer. This Timeline examines the past 25 years of crucial discoveries — from a variety of disciplines — about the components and functions of this pathway.

Imatinib has been an extremely successful treatment for chronic myeloid leukaemia. However, we need to know about the stem cells involved in the disease to understand why relapse is so common when imatinib is stopped.

Changes in the levels of the second messenger Ca²⁺ can result in the activation of broadly proliferative or cytotoxic responses. As reviewed here, to tip the balance in their favour, cancer cells often remodel the expression or activity of their Ca²⁺signalling apparatus.

The causes of metastasis remain elusive. Could the fusion of cancer cells with macrophages or other migratory bone marrow-derived cells (BMDCs) provide an explanation?

This Review discusses the recent progress in the treatment of established (pre)malignant disease of viral or non-viral origin with synthetic long peptide vaccines that are capable of inducing robust T-cell responses.

Most cancer deaths are caused by metastatic spread and subsequent growth of tumour cells at distant organs. How are disseminating tumour cells relevant to the biology of early metastatic spread and how might they be used to improve cancer treatment?

The Mouse Tumor Biology database seeks to facilitate the researcher's access to the ever increasing amount of data now being published using mouse models of cancer. Why is this database important and how does it relate to similar databases within the cancer research community?

Making multidisciplinary translational clinical trials work successfully is complex and challenging. Rakesh Jain presents his perspective on the lessons he and his team have learned from two such trials in patients with advanced rectal cancer or glioblastoma.

This Review examines whether GATA1-related leukaemias in both human and mouse can provide important insights into the mechanism of multi-step leukaemogenesis.

The cyclin-dependent kinase (Cdk) inhibitor p27 regulates cell proliferation, cell motility and apoptosis, and is inactivated through various means in many types of human cancer. Recent studies in several tumour types indicate that p27 expression levels have both prognostic and therapeutic implications.

Testing for prostate-specific antigen is a powerful tool in the detection of prostate cancer, but how should it be used and how can testing be improved to ensure against overdiagnosis?