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Metastasis

Metastasis, the dissemination of tumour cells from a primary site leading to their progressive outgrowth at a distant organ, is ultimately what kills most patients with cancer. Yet, we are only at the cusp of our understanding of the biology of metastasis. For example, we still understand very little about why and how cancer cells migrate and invade away from the primary tumour, the mechanisms regulating cancer cell dormancy at a secondary site, the evolution and heterogeneity of metastatic lesions, why certain cancers metastasize to particular secondary organs (organotropism), and the role played by the modified microenvironment at the distant site in shaping metastatic colonization. Now, various technological developments, increased clinical sample acquisition and improved models are enabling us to overcome the gaps in our knowledge of metastasis with the hope that these conceptual advances might translate into prevention and/or treatment of metastatic disease to improve the survival of patients.

This Collection of the most recently published articles from Nature Reviews Cancer showcases the complexity of the metastatic process and the insights we have gained into the precise molecular and cellular basis of the events that facilitate cancer metastasis. This collection has been produced with exclusive support from HiberCell, Inc. The Collection content is editorially independent and the sole responsibility of Springer Nature.

This Collection is editorially independent, produced with financial support from a third party. About this content.

Reviews

The research autopsy is an underused approach to investigate fundamental questions in cancer biology. This Review discusses the rationale for using research autopsies in cancer research, highlighting how this approach has improved knowledge of cancer biology and its tremendous potential to inform future precision medicine strategies.

Review Article | | Nature Reviews Cancer

Other article types

The abscopal effect, which is the regression of metastatic cancer at distant sites during radiotherapy, is somewhat rare but can be promoted by immunotherapy. This Opinion article describes emerging concepts and limitations of using a combination of radiotherapy and immunotherapy to boost the abscopal effect.

Opinion | | Nature Reviews Cancer

This Analysis article examines the extent of genetic heterogeneity within several types of untreated cancers, with particular regard to its clinical relevance, and finds that the homogeneity of predicted functional mutations in driver genes is the rule rather than the exception.

Analysis | | Nature Reviews Cancer

In this Viewpoint article, we asked four scientists working in the field of epithelial to mesenchymal transition (EMT) to provide their opinions on the role of this complicated phenomenon in cancer biology as well as the challenges of this fast-moving field and the directions it should take in the future.

Viewpoint | | Nature Reviews Cancer

Research Highlights

Two studies provide complementary evidence demonstrating that both endogenous and exogenous antioxidants can induce stabilization of the transcriptional regulator BACH1 to promote lung cancer metastasis.

Research Highlight | | Nature Reviews Cancer

Esposito et al. describe a mechanism for the simultaneous induction of mesenchymal-to-epithelial transition and stem cell traits in disseminating breast cancer cells in the bone, and provide therapeutic opportunities to prevent initiation of bone metastasis.

Research Highlight | | Nature Reviews Cancer

In a study published in Nature, Obradović et al. have identified that breast cancer progression in mice is associated with increased levels of stress hormones resulting in activation of the glucocorticoid receptor at secondary sites, enhanced colonization and decreased survival.

Research Highlight | | Nature Reviews Cancer

Elia et al. show that breast cancer cells in the lung metastatic niche are dependent on pyruvate uptake to promote extracellular matrix remodelling and metastatic growth, which can be targeted therapeutically.

Research Highlight | | Nature Reviews Cancer

Lee et al. show that in a mouse model of melanoma, tumour cells that spread to the draining lymph node adapt to the fatty acid-rich environment in the lymph node by activation of YAP signalling and fatty acid oxidation.

Research Highlight | | Nature Reviews Cancer

Gkountela et al. have identified that circulating tumour cell (CTC) clusters from patients and mouse models with breast cancer have a distinct DNA methylation profile from that of single CTCs, which together with the phenotypic difference represent a targetable therapeutic vulnerability of metastasis.

Research Highlight | | Nature Reviews Cancer

Keklikoglou et al. show that, in mouse models of chemoresistant breast cancer, paclitaxel and doxorubicin trigger the production of tumour-derived extracellular vesicles with pro-metastatic properties that are dependent on annexin A6.

Research Highlight | | Nature Reviews Cancer

Wang et al. demonstrate that increased flux of calcium derived from osteogenic cells into cancer cells promotes early-stage bone colonization. Calcium signalling in cancer cells can be targeted by arsenic trioxide, thereby reducing bone metastasis progression.

Research Highlight | | Nature Reviews Cancer

Two studies from Ashani Weeraratna’s group have examined how changes in the skin microenvironment associated with ageing promote melanoma metastasis and modify immune infiltration.

Research Highlight | | Nature Reviews Cancer

Albrengues et al. have characterized a mechanism by which sustained lung inflammation can cause a switch from cancer dormancy to metastasis through the induction of neutrophil extracellular traps.

Research Highlight | | Nature Reviews Cancer

Yang et al. have used genetically engineered mouse models of small cell lung cancer to show that the same genomic alterations in different cells of origin lead to the formation of tumours that follow distinct evolutionary paths to metastasis.

Research Highlight | | Nature Reviews Cancer

Yao et al. have established that acute lymphoblastic leukaemia cells bypass the need to metastasize via the circulation to the CNS and instead use a direct route migrating along the vascular channels that bridge the bone marrow to the meninges in an α6 integrin-dependent manner.

Research Highlight | | Nature Reviews Cancer