Format

Send to

Choose Destination
Mol Cancer. 2018 Feb 19;17(1):43. doi: 10.1186/s12943-018-0800-6.

Targeting tumour microenvironment by tyrosine kinase inhibitor.

Author information

1
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
2
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA.
3
School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China. yfeng@hku.hk.
4
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA. yfeng@hku.hk.
5
Department of Pharmacology, Yale University School of Medicine, New Haven, CT, USA. yccheng@yale.edu.

Abstract

Tumour microenvironment (TME) is a key determinant of tumour growth and metastasis. TME could be very different for each type and location of tumour and TME may change constantly during tumour growth. Multiple counterparts in surrounding microenvironment including mesenchymal-, hematopoietic-originated cells as well as non-cellular components affect TME. Thus, therapeutics that can disrupt the tumour-favouring microenvironment should be further explored for cancer therapy. Previous efforts in unravelling the dysregulated mechanisms of TME components has identified numerous protein tyrosine kinases, while its corresponding inhibitors have demonstrated potent modulatory effect on TME. Recent works have demonstrated that beyond the direct action on cancer cells, tyrosine kinase inhibitors (TKIs) have been implicated in inactivation or normalization of dysregulated TME components leading to cancer regression. Either through re-sensitizing the tumour cells or reversing the immunological tolerance microenvironment, the emergence of these TME modulatory mechanism of TKIs supports the combinatory use of TKIs with current chemotherapy or immunotherapy for cancer therapy. Therefore, an appropriate understanding on TME modulation by TKIs may offer another mode of action of TKIs for cancer treatment. This review highlights mode of kinase activation or paracrine ligand production from TME components and summarises the findings on the potential use of various TKIs on regulating TME components. At last, the combination use of current TKIs with immunotherapy in the perspectives of efficacy and safety are discussed.

KEYWORDS:

Immunotherapy; Tumour microenvironment; Tyrosine kinase inhibitors

PMID:
29455663
PMCID:
PMC5817793
DOI:
10.1186/s12943-018-0800-6
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center