Targeting tumour microenvironment by tyrosine kinase inhibitor

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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.



https://molecular-cancer.biomedcentral. ... 018-0800-6

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TME shows a composition of tumor tissue, which consists of immune cells, adipocytes, lymphatic endothelial cells, extracellular matrix (ECM), glial cells, activated fibroblasts, pericytes, epithelial cells, vascular cells, and proteins [21,39].

https://www.sciencedirect.com/topics/me ... nvironment

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“No man is an island – we exist together with other people in families, communities and societies. The same is true of cancer cells – they need a host of non-cancerous cells, collectively known as the tumour microenvironment, to help them grow and develop.


In the latest of our Expert Opinion interviews we talk with Professor Fran Balkwill, who argues that treating the tumour and its microenvironment together represents an exciting frontier for cancer treatment.“

https://scienceblog.cancerresearchuk.or ... -balkwill/