Reviews & Analysis

Proteases have long been associated with cancer progression and metastasis, however studies have also revealed proteases with tumour-suppressive effects. What are the implications of these findings?

Oestrogen receptor-a (ERa)-regulated transcription in breast cancer cells involves protein co-factors that contribute to the regulation of chromatin structure. How do these relate with ER activity and potentially with the activity of breast cancer drugs, including tamoxifen?

Advances in antibody engineering make it possible to produce various recombinant proteins that exploit the specificity of the antibody- combining site to manipulate tumour-related signalling, and to stimulate anti-tumour immune responses. but can we improve antibodies further to fully engage the tumour immune response?

Breast cancer is not a single disease, but is instead a collection of diseases that have distinct histopathological features, genetic and genomic variability, and diverse prognostic outcomes. What is the most powerful way to investigate this heterogeneous disease?

The myeloproliferative disorders (MPD) polycythaemia vera (PV), essential thombocythaemia (ET), and primary myelofibrosis (PMF) are clonal disorders of multipotent haematopoietic progenitors, and most patients with these diseases acquire a single point mutation in the cytoplasmic tyrosine kinase JAK2 (JAK2V617F). What are the implications of these findings for MPD?

This Perspective discusses the feasibility of identifying oncoantigens (proteins required for tumour progression) using mouse models and human mRNA profiling data. Will such oncoantigens make good cancer vaccine targets?

Animal models of cancer are an immense resource for cancer medicine, but only now are we realising their full potential. What new approaches are needed to derive the maximum value for cancer patients from mouse models of cancer?

Accumulating evidence indicates that the active metabolite of vitamin D, 1α,25(OH)₂D₃, or vitamin D analogues might have potential as anticancer agents because their administration has antiproliferative effects, can activate apoptotic pathways and inhibit angiogenesis. What are the possibilities for 1α,25(OH)₂D₃and vitamin D analogues as preventative and therapeutic anticancer agents?

Alcohol is one of the most widely consumed toxic substances, and approxmiately 3.6% of cancers result from chronic alcohol drinking. What are some of the mechanisms by which alcohol acts as a carcinogen?

Multiple myeloma is an incurable B-cell malignancy that is actively sustained by the bone marrow microenvironment. Targeting myeloma cells and their bone marrow interactions seems a promising strategy to overcome drug resistance and improve patient outcome.

Irreversible covalent inhibitors equipped with reporter groups allow the study of target enzymes based on catalytic activity instead of expression level. This Perspective discusses the design and use of such probes directed at the ubiquitin–proteasome system. Can they identify new cancer therapies that target this system?

Cisplatin was first used for cancer therapy in the 1970s. Interest in platinum drugs has been revived recently: new agents have been developed, a better understanding of resistance mechanisms has been gained, and combination trials with resistance modulators and targeted agents have been initiated.

This article examines whether heterochromatic instability might explain the loss of the heterochromatic inactive X chromosome (Barr body) in some breast and ovarian cancers. Might this mechanism have wider implications for the evolution of some cancer types?

A role for oestrogen has been implicated in the development of prostate cancer, but this role is complex. Should selective oestrogen-receptor modulators in conjunction with contemporary androgen-ablation therapy be used to treat this disease?

Altered expression of specific Ca²⁺ channels and pumps are characterizing features of some cancers. The ability of Ca²⁺ to regulate both cell death and proliferation, combined with the potential for pharmacological modulation, offers the opportunity for a set of new drug targets in cancer. Which Ca²⁺channels and pumps should be targeted and what strategy should be used?

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?

The advent of microarray technology has led to a flurry of gene-expression profiling studies aimed at defining patients into more clinically-relevant groups at the same time as gaining new insights into cancer pathology. This is particularly evident for breast cancer research. What are the current limitations and future prospects for the translation of molecular signatures?

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?

The protein kinase C family of serine/threonine kinases is implicated in tumorigenesis. Although targeting these kinases for cancer therapy is not a new idea, the results from clincal trials with several agents have been disapointing. Why is this?