Acta Pharmaceutica Sinica B

Acta Pharmaceutica Sinica B

Volume 5, Issue 5, September 2015, Pages 402-418
Acta Pharmaceutica Sinica B

REVIEW
Cancer metastases: challenges and opportunities

https://doi.org/10.1016/j.apsb.2015.07.005Get rights and content
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open access

Abstract

Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Although cancer survival rate has been significantly improved over the years, the improvement is primarily due to early diagnosis and cancer growth inhibition. Limited progress has been made in the treatment of cancer metastasis due to various factors. Current treatments for cancer metastasis are mainly chemotherapy and radiotherapy, though the new generation anti-cancer drugs (predominantly neutralizing antibodies for growth factors and small molecule kinase inhibitors) do have the effects on cancer metastasis in addition to their effects on cancer growth. Cancer metastasis begins with detachment of metastatic cells from the primary tumor, travel of the cells to different sites through blood/lymphatic vessels, settlement and growth of the cells at a distal site. During the process, metastatic cells go through detachment, migration, invasion and adhesion. These four essential, metastatic steps are inter-related and affected by multi-biochemical events and parameters. Additionally, it is known that tumor microenvironment (such as extracellular matrix structure, growth factors, chemokines, matrix metalloproteinases) plays a significant role in cancer metastasis. The biochemical events and parameters involved in the metastatic process and tumor microenvironment have been targeted or can be potential targets for metastasis prevention and inhibition. This review provides an overview of these metastasis essential steps, related biochemical factors, and targets for intervention.

Graphical abstract

Cancer metastasis is the major cause of cancer morbidity and mortality, and accounts for about 90% of cancer deaths. Limited progress has been made in the treatment of cancer metastasis due to various factors. This review is aimed to provide an overview of the metastasis process and targets for intervention with a focus on cancer cell detachment, migration, invasion and adhesion. It is hoped that this review can serve as a lead for readers who are interested in cancer metastasis and intervention.

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Abbreviations

BM
basement membrane
CAFs
cancer-associated fibroblasts
CAMs
cell adhesion molecules
CAT
collective amoeboid transition
CCL2
chemokine (C–C motif) ligand 2
CCR3
chemokine receptor 3
Col
collagen
COX2
cyclooxygenase 2
CSF-1
chemokine colonystimulating factor–1
CTGF
connective tissue growth factor
CXCR2
chemokine receptor type 2
DISC
death-inducing signaling complex
ECM
extracellular matrix
EGF
epidermal growth factor
EGFR
EGF receptor
EMT
epithelial–mesenchymal transition
FAK
focal adhesion kinase
FAs
focal adhesions
FGF
fibroblast growth factor
FN
fibronectin
HA
hyaluronan
HGF
hepatocyte growth factor
HIFs
hypoxia-inducible factors
IKK
IκB kinase
JAK
the Janus kinases
LN
laminin
MAPK
mitogen-activated protein kinase
MAT
mesenchymal to amoeboid transition
MET
mesenchymal–epithelial transition
MMPs
matrix metalloproteinases
PDGF
platelet-derived growth factor
PI3K
phosphatidylinositol 3-kinase
STATs
signal transducers and activators of transcription
TAMs
tumor-associated macrophages
TGF-β
transforming growth factor β
TME
tumor microenvironment
VCAMs
vascular cell adhesion molecules
VEGF
vascular endothelial growth factor
VN
vitronectin

KEY WORDS

Metastasis
Detachment
Migration
Invasion
Adhesion
Cancer

Cited by (0)

Peer review under responsibility of Institute of Materia Medica, Chinese Academy of Medical Sciences and Chinese Pharmaceutical Association.