Reviews & Analysis

A significant problem in cancer biology is determining the functions of uncharacterized cancer-associated genes discovered from genomic and proteomic datasets. This Review explores how cancer-gene function can be deduced using computational and statsitical methods.

Phenomics is the systematic and meticulous collection, objective documentation and cataloguing of phenotypic data at many levels. This Review describes the possible uses of phenomics in cancer research, using the examples ofRET and PTENphenomics.

Some cytochrome P450 (CYP) enzymes participate in the detoxication of xenobiotics and, paradoxically, can form reactive intermediates that can damage DNA, lipids and proteins. What function do these enzymes have in carcinogenesis driven by the environment?

Understanding p53 regulation remains a crucial goal to design broadly applicable anticancer strategies that target this pathway. In this context, this Review analyses the function of p53 post-translational modifications and the p53 regulators MDM2 and MDM4 using recentin vitro and in vivodata.

The hormone gastrin has a central role in gastric acid secretion and is associated with malignant progression in transgenic mouse models. Does gastrin participate in human gastric cancers or is it merely a bystander?

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?

The peptidome is the range of low-molecular-weight peptides found in the bloodstream, and seems to differ between patients with and without cancer. How can the peptidome best be studied, and can it be used for cancer diagnostics?

There is evidence that apart from its ability to regulate the transcriptional activity of β-catenin, adenomatus polyposis coli (APC) has β-catenin-independent functions. Is the interaction of APC with cytoskeletal components important for cancer development and progression in the gut?

Polycomb group (PcG) proteins are epigenetic gene silencers that are implicated in neoplastic development. How do PcGs regulate cellular identity, and how might these functions be relevant during tumorigenesis?

Research on microRNAs in cancer is moving apace. This Review discusses why miRNA profiling is proving to be a useful new tool for identifying tumour subtypes, and can accurately predict patient outcome. Could miRNAs be exploited to treat tumours?

Clinical trials have shown that tumours have a modest response to EGFR inhibitors when used alone. Will they prove to be more effective when combined with radiotherapy or chemotherapy or both?

Most premenopausal women diagnosed with primary breast cancer receive adjuvant chemotherapy, and many experience chemotherapy-induced ovarian failure (CIOF). Can inherited genetic factors and a better understanding of the biology of CIOF be used to provide optimal counselling for these women?

Given the lack of progress in curing metastatic epithelial cancers, there is intense interest in cancer chemoprevention strategies. However, the serious side effects that have been identified in some cancer prevention trials underscore the need to re-evaluate our approach to clinical chemopreventative drug development.

The number of circulating endothelial cells and their progenitors is increased in some types of cancer, and there is evidence that aspects of these cells might correlate with clinical outcome of cancer patients treated with anti-angiogenic drugs.

The FDA recently approved a human papillomavirus preventive vaccine for cervical cancer, the second largest cause of cancer deaths in women. How will the introduction of this vaccine affect cervical cancer incidence and what are the outstanding issues?

Nuclear DNA topoisomerase I (TOP1) is an essential human enzyme, and is the only known target of the camptothecin and its derivatives. The mechanisms and molecular determinants of the tumour response to TOP1 inhibitors are reviewed in the context of developing camptothecin and non-camptothecin derivatives that further increase anti-tumour activity but also reduce side effects.

Most cancer patients who are treated with epidermal growth factor receptor inhibitors (EGFRIs) develop dermatological toxicities owing to the important function of the EGFR signalling pathway in the skin. How do EGFRIs affect the skin and what treatments are needed to avoid these undesirable side effects?

The US National Cancer Institute (NCI) 60 human tumour cell line anticancer drug screen (NCI60) was developed nearly 20 years ago, and is a valuable source of information about anticancer drug leads and mechanisms of growth inhibition.

Cysteine cathepsins are proteolytic enzymes whose expression is increased in both tumour and tumour-associated cells. What is known about the extracellular and intracellular functions of these enzymes in cancer?

Ubiquitin and ubiquitin-like proteins (Ubls) participate in many cellular processes, such as apoptosis and DNA repair. How can the deregulation of ubiquitin and Ubls lead to cancer formation, and how might ubiquitin and Ubl pathways be targeted by anticancer therapeutics?