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Derailed endocytosis: an emerging feature of cancer

Nature Reviews Cancer 8, 835 (2008). doi:10.1038/nrc2521

Authors: Yaron Mosesson, Gordon B. Mills & Yosef Yarden

Once engaged by soluble or matrix-anchored ligands, cell surface proteins are commonly sorted to lysosomal degradation through several endocytic pathways. Defective vesicular trafficking of growth factor receptors, as well as unbalanced recycling of integrin- and cadherin-based adhesion complexes, has emerged in the past 5 years

Ageing, oxidative stress and cancer: paradigms in parallax

Nature Reviews Cancer 8, 875 (2008). doi:10.1038/nrc2522

Authors: Christopher C. Benz & Christina Yau

Two paradigms central to geroscience research are that aging is associated with increased oxidative stress and increased cancer risk. Therefore, it could be deduced that cancers arising with ageing will show evidence of increased oxidative stress. Recent studies of gene expression in age-controlled breast cancer

Genetics: ALK takes the rap

Nature Reviews Cancer 8, 833 (2008). doi:10.1038/nrc2529

Author: Nicola McCarthy

Like retinoblastoma, neuroblastoma can be an inherited or a sporadic tumour but, unlike retinoblastoma, the genetics underlying neuroblastoma development have remained for the most part enigmatic. Four papers published in Nature have now found at least one major culprit — the anaplastic lymphoma kinase

Tumorigenesis: Keeping a watchful eye

Nature Reviews Cancer 8, 829 (2008). doi:10.1038/nrc2530

Author: Safia Ali Danovi

Disruptions in the delicate balance between keratinocyte proliferation and differentiation can contribute towards the development of squamous cell carcinoma (SCC) of the skin — a common human malignancy. It has been proposed that innate surveillants, molecules that promote terminal keratinocyte differentiation, exist in the skin

Immunology: An unexpected complement

Nature Reviews Cancer 8, 827 (2008). doi:10.1038/nrc2531

Author: Sarah Seton-Rogers

Depending on the context, the immune system can both promote and inhibit tumour growth. The complement system has been proposed to enhance the efficacy of anticancer monoclonal antibody therapy, but there has been little research into the potential tumour-promoting ability of complement. John Lambris and

Metastasis: A sweet sabre promotes cell invasion

Nature Reviews Cancer 8, 828 (2008). doi:10.1038/nrc2532

Author: Mirko von Elstermann

Tumour cells invade their surrounding tissue and degrade the extracellular matrix (ECM) glycosaminoglycan component hyaluronan. Hyaluronan fragments can also promote tumour cell invasion through a mechanism involving the cell surface glycoprotein CD44. Reporting in Cancer Research, Sugahara et al. show that specific

Radiotherapy: Worming your way to cell death

Nature Reviews Cancer 8, 830 (2008). doi:10.1038/nrc2533

Author: Gemma K. Alderton

The mechanisms underlying radiation-induced cell death remain somewhat controversial. One suggestion is that ceramide functions as a crucial transducer of apoptosis after exposure to ionizing radiation. However, until now, evidence for a direct link between ceramide synthesis and apoptosis pathways has been lacking. Xinzhu Deng

Trial watch

Nature Reviews Cancer 8, 828 (2008). doi:10.1038/nrc2534

Inhibiting survivinA phase I, first-in-human study of YM155, a small-molecule inhibitor of the anti-apoptosis protein survivin, has indicated that the drug can be safely administered and might have anti-tumour activity.A range of YM155 doses were administered for 127 cycles to 41 patients who

From the editors

Nature Reviews Cancer 8, 825 (2008). doi:10.1038/nrc2535

It is a truth universally acknowledged that the human papillomavirus (HPV) causes cervical cancer. Yet such a statement would have ruffled more than a few feathers in the 1970s when the prevailing belief was that this sexually transmitted gynaecological malignancy was the work of the

Vitamin C: friend or foe?

Nature Reviews Cancer 8, 830 (2008). doi:10.1038/nrc2537

Author: Isobel Barry

Controversy has dogged the use of vitamin C supplements during cancer therapy, and research from the Memorial Sloan-Kettering Cancer Center has brought this once more into the public eye.A preclinical study has shown that pretreatment of tumour cells with dehydroascorbic acid has a protective

In Brief

Nature Reviews Cancer 8, 831 (2008). doi:10.1038/nrc2538

TumorigenesisPreneoplastic lesion growth driven by the death of adjacent normal stem cellsChao, D. L., Eck, J. T., Brash, D. E., Maley, C. C. & Luebeck, E. G.Proc. Natl Acad. Sci. USA105,

The von Hippel–Lindau tumour suppressor protein: O2 sensing and cancer

Nature Reviews Cancer 8, 865 (2008). doi:10.1038/nrc2502

Author: William G. Kaelin Jr

The von Hippel–Lindau disease is caused by inactivating germline mutations of the VHL tumour suppressor gene and is associated with an increased risk of a variety of tumours in an allele-specific manner. The role of the heterodimeric transcription factor hypoxia-inducible factor (HIF) in the

VEGF-A splicing: the key to anti-angiogenic therapeutics?

Nature Reviews Cancer 8, 880 (2008). doi:10.1038/nrc2505

Authors: Steven J. Harper & David O. Bates

The physiology of microvessels limits the growth and development of tumours. Tumours gain nutrients and excrete waste through growth-associated microvessels. New anticancer therapies target this microvasculature by inhibiting vascular endothelial growth factor A (VEGF-A) splice isoforms that promote microvessel growth. However, certain VEGF-A splice isoforms

Metastasis: Preparing the soil

Nature Reviews Cancer 8, 832 (2008). doi:10.1038/nrc2525

Author: Sarah Seton-Rogers

Before tumour cells metastasize, it seems that chemoattractants induce the accumulation of macrophages and haematopoietic progenitor cells in distant organs. Yoshiro Maru and colleagues have delineated a pathway that could be important in this process.Previous work by the authors showed that distant primary tumours

Angiogenesis: Multipotent tumour endothelial cells

Nature Reviews Cancer 8, 828 (2008). doi:10.1038/nrc2526

Author: Meera Swami

New blood vessels are required for the growth of tumours, but tumour blood vessels are poorly formed and dysfunctional. Can the properties of tumour endothelial cells (TECs) help us to understand abnormalities in tumour blood vessel formation? A recent study has shown that TECs isolated

Tumorigenesis: It's a knockout!

Nature Reviews Cancer 8, 832 (2008). doi:10.1038/nrc2527

Author: Safia Ali Danovi

Advocates of a tumour-suppressive function for the p53 homologue TAp73 breathed a collective sigh of relief following the recent analysis of a TAp73-specific knockout mouse.Efforts to dissect the role of this protein in cancer have been hampered by the fact that the Trp73

Hypoxia signalling through mTOR and the unfolded protein response in cancer

Nature Reviews Cancer 8, 851 (2008). doi:10.1038/nrc2501

Authors: Bradly G. Wouters & Marianne Koritzinsky

Hypoxia occurs in the majority of tumours, promoting angiogenesis, metastasis and resistance to therapy. Responses to hypoxia are orchestrated in part through activation of the hypoxia-inducible factor family of transcription factors (HIFs). Recently, two additional O2-sensitive signalling pathways have also been implicated: signalling

Cytokines and their relationship to the symptoms and outcome of cancer

Nature Reviews Cancer 8, 887 (2008). doi:10.1038/nrc2507

Authors: Bostjan Seruga, Haibo Zhang, Lori J. Bernstein & Ian F. Tannock

Tumours contain immune cells and a network of pro- and anti-inflammatory cytokines, which collaborate in the development and progression of cancer. Cytokine profiles might prove to be prognostic. The systemic effects of pro-inflammatory cytokines are associated with fatigue, depression and cognitive impairment, and can affect

Opinions regarding cord blood use need an update

Nature Reviews Cancer 8, 823 (2008). doi:10.1038/nrc2418-c1

Author: J. J. Nietfeld

The recent Perspective by Sullivan (Sullivan, M. J. Banking on cord blood stem cells. Nature Rev. Cancer8, 555–563 (2008)) states that information on cord blood (CB) banking that is provided for parents “needs to be scientifically accurate”. Unfortunately, the Perspective

Cord blood stem cells: worth the investment

Nature Reviews Cancer 8, 823 (2008). doi:10.1038/nrc2418-c2

Author: David T. Harris

Nature Reviews Cancer recently published a commentary by M. J. Sullivan, expressing an opinion on the value of umbilical cord blood stem cells and cord blood preservation options, that contained a number of errors (Sullivan, M. J. Banking on cord blood stem cells.