Opinion in 2012

Despite displaying characteristics of tumour suppressors, the core regulators of epithelial cell polarity are rarely mutated in tumours, and it is still unclear whether they directly contribute to cancer development. However, data from human tumour viruses provide compelling evidence of a central role for the perturbation of cell polarity in cancer.

Although the roles of individual phospholipases and their lipid mediators in cancer have been studied extensively, it is less clear how these enzymes interact with each other and other cellular pathways to affect cancer-associated processes. This Opinion article argues that a thorough understanding of phospholipase signalling networks is necessary to determine whether these enzymes can be targeted therapeutically.

Despite recent advances, the acute and long-term morbidity of current curative therapies can be substantial, and several childhood cancers still have unacceptably low cure rates. Does the development of molecularly targeted anticancer drugs offer the prospect of more effective therapy for childhood cancers?

This article outlines some of the issues surrounding the terminology used for cancer stem cells (CSCs) and how CSCs are defined, with an aim to develop a consensus. More precise reporting of parameters used to identify CSCs is also recommended to enhance our understanding of CSC biology and to ultimately eradicate these cells in patients.

As part of our Series of articles on The next 10 years in cancer research, this Opinion article discusses what the future may hold for angiogenesis inhibitors as cancer therapeutics.

Individuals with Down's syndrome have an increased risk of developing leukaemia in childhood, but they also have a significantly reduced risk of developing most solid tumours. However, Down's syndrome shares many features with cancer-prone syndromes, so why is Down's syndrome different?

Chromatin conformation and chromatin modifications affect DNA damage response signalling and hence the associated cellular outcomes of this response. This Opinion article discusses the implications of chromatin alterations in cancer cells on DNA damage responses.

NFE2-related factor 2 (NRF2) has apparently contradictory roles in cancer. Activation of NRF2 contributes to the chemopreventive effects of various clinically used drugs against various diseases including cancer. However, NRF2 activity can also accelerate tumorigenesis in mouse models, thus highlighting a potential danger of NRF2 activation. This Opinion article discusses how these opposing roles might be reconciled.

How many of the changes identified in human cancer by genome sequencing are meaningful? And how can we exploit these massive data sets to yield new therapeutic targets? This article outlines five approaches that aim to discover oncogenic drivers, tumour dependencies and, ultimately, new cancer therapies from cancer genome data.

This Opinion article discusses how alterations to epigenetic programmes during development (including in the uterus), which may arise from exposure to hormones, can increase the risk of developing metabolic diseases and cancer in adulthood.

All malignant cancers, whether inherited or sporadic, are fundamentally governed by Darwinian dynamics and consist of dynamically evolving clades of cells living in distinct microhabitats that almost certainly ensure the emergence of therapy-resistant populations. However, the principles of Darwinian dynamics also embody fundamental principles that can be used for the successful management of cancer.

Drug resistance is a common cause of treatment failure for HIV infection and cancer. Can HIV therapy provide a 'blueprint' for designing and validating patient-specific combination therapies in cancer?

Why are many metastases differentiated? This Opinion article proposes that this is due to phenotypic plasticity involving transient epithelial–mesenchymal transition (EMT). In undifferentiated metastasis, it might be that cells are genetically locked into an undifferentiated state. The therapeutic consequences of this hypothesis are also discussed.

Cannabinoids have well-established roles in palliating cancer-associated symptoms, but numerous recent studies also support their antitumorigenic activity. This Opinion article focuses on preclinical studies of the antitumour effects of cannabinoids, including the associated cellular signalling pathways and resistance mechanisms.

The infiltration of various types of immune cells is common to most tumour microenvironments. As discussed in this Opinion article, the pattern of immune cell infiltration varies between cancer type and individual tumours of the same type, and this pattern can be used to indicate prognosis and response to therapy.

Cytotoxic T lymphocyte-associated antigen 4 (CTLA4) represents a crucial immune checkpoint, the blockade of which can potentiate anti-tumour immunity. This treatment in patients with advance prostate cancer may provide insights into the targets that the immune system recognizes to drive tumour regression.

Tumours often engage the lymphatic system to invade and metastasize. This Opinion article proposes that increased interstitial and lymphatic flow in the tumour microenvironment, and the resulting mechanical changes to the tumour stroma, may strongly alter host immunity to the tumour.

The RB family is usually associated with the regulation of the G1/S transition and cell cycle entry. Recent data have shown a role for the RB family in regulating S phase and mitosis, which has implications for the genomic stability of tumour cells in which the RB family is inactivated.

Although mouse models have improved our understanding of cancer biology, their inbred nature does not accurately model the inherited variability in human populations that can influence cancer susceptibility and outcomes. This Opinion article discusses how inherited variability influences cancer phenotypes, how it can confound experiments and how it can be exploited to reveal new truths about cancer biology.