Review Articles in 2007

Cell division cycle 25 (CDC25) phosphatases regulate key cell-cycle transitions. Thus, it is not surprising that CDC25 overexpression has been reported in a significant number of human cancers. What are the roles of CDC25 phosphatases in abnormal cell proliferation, and what is the future for targeting CDC25 activity in cancer treatment?

Can the process of new cancer-preventive drug development be improved by focusing on precancer (intraepithelial neoplasia) to better identify subjects at risk and prove efficacy in shorter, smaller trials?

Inactivation of cancer-relevant genes through DNA methylation is a common event in tumours, including genitourinary cancers. The clinical implementation of gene methylation screenings could provide a new avenue for the early detection of genitourinary cancers, which are increasing worldwide. What are the current challenges?

We are all familiar with the concept of morphogens instructing tissue architecture during development, but how are tissue form and function maintained in the adult, and does this have a bearing on tumorigenesis?

Metastatic capacity appears to be an inherent feature of breast tumours. In this context, the cofilin pathway has been identified as a major determinant of metastasis and, as discussed in this Review, studies indicate that the overall activity of the cofilin pathway determines the invasive and metastatic phenotype of tumour cells.

What leads to the incurable advanced phase of chronic myeloid leukaemia (CML)? This Review explores the mechanisms that underlie differentiation arrest, genomic instability and loss of tumour-suppressor function, which seem to drive the progression to blast crisis in CML and might help to identify new therapeutic targets. These findings can potentially be translated to other tumours that progress through similar mechanisms.

Nucleic acids and regulatory proteins are compartmentalized in microenvironments within the nucleus. These precise arrangements can be distrupted in cancer cells. How can we measure these changes and what might they tell us about cancer development and treatment?

This article reviews how the identification of Snail, ZEB and some basic helix–loop–helix (bHLH) factors as inducers of epithelial–mesenchymal transition (EMT) and potent repressors of E cadherin expression has opened new avenues for cancer research with potential clinical implications.

Imatinib is a highly effective treatment for chronic myeloid leukaemia. However, patients often develop resistance to this ABL kinase inhibitor. This Review discusses second generation inhibitors of ABL and other signalling pathways that might help circumvent imatinib resistance.

The basement membrane molecule laminin 332 (previously known as laminin 5) activates various signalling pathways and interacts with other basement membrane components to promote squamous-cell carcinoma (SCC) development. How does laminin 332 coordinate SCC tumorigenesis and can it be targeted therapeutically?

Although inhibition of tyrosine kinases has revolutionized cancer therapy, some of the inhibitors used have now been associated with cardiotoxicity. How does inhibition of cancer-relevant signalling pathways affect heart cells, and how can these effects be minimized?

Synthetic oleanane triterpenoids and rexinoids are two new classes of multifunctional drugs. Both classes of agents can prevent and treat cancer in experimental animals. What promise do they hold for cancer prevention and treatment in humans?

The peptidyl-prolyl isomerase PIN1 regulates a number of proteins important for cell-cycle progression, therefore it seems logical that alterations in PIN1 activity could be involved in tumorigenesis. But is loss or gain of function important?

HTLV-1 causes adult T-cell leukaemia (ATL). The HTLV-1 Tax protein, which affects multiple cellular pathways, is required to transform cells. What are the molecular mechanisms of leukaemogenesis by Tax and other HTLV-1 genes?

Ras genes are the most common targets for somatic gain-of-function mutations in human cancer. Germline mutations that affect components of the Ras signalling pathway were shown to cause several developmental disorders. What are the implications of germline mutations in the Ras pathway for our understanding of normal developmental processes and cancer pathogenesis?

Since the discovery of protein kinase C (PKC) in the 1980s, we still have only a partial understanding of how this family of serine/threonine kinases is involved in tumour promotion. What do we still need to learn and what about the other proteins known to respond downstream of the PKC activator diacylglycerol?

Aggressive tumour cells share many characteristics with embryonic stem cells, contributing to the conundrum of tumour cell plasticity. This review discusses the evidence for the convergence of embryonic and tumorigenic signalling pathways, highlighting the most prominent targets that could be therapeutically beneficial.

Recent evidence indicates that both endogenous and environmental factors induce prostate inflammatory lesions that are proposed to increase the risk of cancer development. This Review explores different approaches aimed at clarifying whether inflammation drives prostate cancer and could be used to develop new prevention strategies.

Gene fusions are generally thought to be causally associated with sarcomas and haematological cancers, but recent evidence has shown that they occur in all malignancies, and account for 20% of human cancer morbidity. This Review discusses the implications of this for cancer research.

The lessons learned from the clinical application of epidermal growth factor receptor tyrosine kinase inhibitors provide important insights for lung cancer therapies. What approaches might circumvent the rapid acquisition of resistance and increase the efficacy of targeted therapies in lung cancer and other epithelial cancers?