Metastasis

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.

This Review discusses how circulating tumour cell (CTC) analysis at single-cell resolution provides unique insights into tumour heterogeneity that are not revealed by analysis of circulating tumour DNA (ctDNA) derived from liquid biopsies.

Therapeutic strategies in malignant melanoma are challenged by resistance mechanisms that are based on phenotype plasticity. This Review discusses different phenotypes in melanoma, how they are controlled and how phenotype plasticity contributes to melanoma progression and therapy resistance.

In this Review, Altorki et al. discuss how the tumour-reprogrammed lung microenvironment can contribute to primary lung tumour progression as well as lung metastasis from extrapulmonary neoplasms by promoting inflammation, angiogenesis, immune modulation and therapeutic responses.

In this Review, Hamidi and Ivaska discuss the contribution of integrins to the different steps of cancer progression, highlighting some of the recently identified unconventional roles of integrins and novel opportunities to target integrin signalling.

In this Review, Stueltenet al. outline insights with relevance to human cancer invasion and metastasis that have come from the study of cell motility in non-mammalian model organisms.

In this Review, Hunteret al. discuss how genetic heterogeneity impacts metastatic disease and outline the implications of our current knowledge in this area for future research efforts and therapeutic interventions.

This Review summarizes the natural progression of pre-metastatic niche formation and evolution, highlighting recent advances and future hurdles.

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.

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.

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.

In this Perspectives article, the authors outline the preclinical and clinical evidence for epithelial–mesenchymal plasticity (EMP) in cancer progression and metastasis, focusing on recent challenges and controversies, and highlight strategies to therapeutically target the EMP process.

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.

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.

Benbenishty et al. find that prophylactic administration of CpG-C, a Toll-like receptor 9 agonist, significantly reduces the development of brain metastasis in preclinical mouse models via the activation of microglial cells that kill and phagocytose the tumour cells.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.