Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion. Intratumoral hypoxia and genetic alterations can lead to HIF-1alpha overexpression, which has been associated with increased patient mortality in several cancer types. In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth. Efforts are underway to identify inhibitors of HIF-1 and to test their efficacy as anticancer therapeutics.

Targeting HIF-1 for cancer therapy

Researchers have been studying metastasis for more than 100 years, and only recently have we gained insight into the mechanisms by which metastatic cells arise from primary tumours and the reasons that certain tumour types tend to metastasize to specific organs. Stephen Paget's 1889 proposal that metastasis depends on cross-talk between selected cancer cells (the 'seeds') and specific organ microenvironments (the 'soil') still holds forth today. It is now known that the potential of a tumour cell to metastasize depends on its interactions with the homeostatic factors that promote tumour-cell growth, survival, angiogenesis, invasion and metastasis. How has this field developed over the past century, and what major breakthroughs are most likely to lead to effective therapeutic approaches?

https://www.nature.com/articles/nrc1098.pdf?proof=t

The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited

Cancer Metastasis: Building a Framework

The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies.

/pdf/tumour-stem-cells-and-drug-resistance-210hrtgy2n.pdf

Tumour stem cells and drug resistance

Tumor Metastasis: Molecular Insights and Evolving Paradigms

Retention of “metastatic” colonisation potential by cells of spontaneous primary tumours after cryopreservation

Retention of "metastatic" colonisation potential by cells of spontaneous primary tumours after cryopreservation.

Tumorigenicity and metastatic behavior in nude mice of two human squamous cell carcinoma lines that differ in production of the cytokine ETAF/IL-1

Metastatic disease, mainly to the lungs, liver, bone, and brain, is the most common cause of death from breast cancer, despite advances in surgical and clinical management. Two basic principles govern the process of metastasis. First, that tumors are heterogeneous populations of cells, and second, that the process is a sequence of events that depends on tumor cell properties and interactions with the microenvironment at the site of metastasis. Inhibitors targeted at any of these different steps have the potential to inhibit metastatic progression, and examples of key therapeutic targets include overexpression of growth factor receptors, angiogenic factors, matrix metalloproteases, and integrin receptors. The identification of molecular targets for therapy of breast cancer metastasis will be accelerated by DNA array technology, and their selection for use should include evaluation of interactions between tumor cells and normal tissue components. These sorts of inhibitors are likely to target both cancer and normal cell functions, for example, inhibitors of matrix metalloproteases that can potentially inhibit both tumor cell invasion and angiogenesis. The use of appropriate animal models will be necessary to determine the impact of targeted inhibitors on the growth and development of breast cancer metastasis.

Janet E. Price

Papers

Retention of "metastatic" colonisation potential by cells of spontaneous primary tumours after cryopreservation.

Tumorigenicity and metastatic behavior in nude mice of two human squamous cell carcinoma lines that differ in production of the cytokine ETAF/IL-1

Therapeutic intervention with breast cancer metastasis.

Lectin agglutinability of mammary tumours with differing metastatic colonisation potentials.

Molecular profile of advanced-stage transitional cell carcinoma of the ovary ☆ ☆☆ ★