Understand the acquired resistance of RTK inhibitors by computational receptor tyrosine kinases network.

Abstract:

:Receptor Tyrosine Kinase inhibitors are the most popular anti-cancer drug types. But the resistance is the major challenge. Our study on the network with 1334 proteins and their 2623 interactions which retrieved from 52 RTKs indicated that most RTKs proteins were the key controllers of the protein-protein network. Direct or indirect interactions with RTKs (shortest path of 2) were often associated with resistance to RTKs inhibitors in the literature. The results based on the KEGG pathway analysis demonstrated the Rap1 signal pathway would also contribute to the resistance of RTKs inhibitor as well as the known Ras pathway and PI3K/Akt pathway. The pathways can crosstalk within and between complex signals transduction networks, then activate the upstream or downstream pathway, and/or activate the other oncogenes, which lead to the acquired resistance. Our results gave a systematically global view to understand the drug resistance and provided a clue to how to combine the different targets or pathways for synergy of targeted RTKs inhibitors.

journal_name

Comput Biol Chem

authors

Tian Y,Ma Y,Wu S,Zhang T,Li Z,Wang G,Zhang J

doi

10.1016/j.compbiolchem.2018.07.017

subject

Has Abstract

pub_date

2018-10-01 00:00:00

pages

275-282

eissn

1476-9271

issn

1476-928X

pii

S1476-9271(17)30293-1

journal_volume

76

pub_type

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