Hyper-activation of the HER family receptors, leads to up-regulation of the three vital signaling pathways, such as PI3K-AKT or MAPK pathways. It has been demonstrated that one of the reason for resistant development to anti-cancer therapeutic agent, such as trastuzumab, can be HER2 dimerization and/ or formation of heterodimer between HER family receptors.
However, the overexpressed HER family receptors may for heterodimers or co-expressed with some other receptors in breast cancer cells and subsequently cause the development of resistance. For example, HER2 and IGFR-1 heterodimeriztion in breast cancer may have significant role in resistance to therapeutic agents.
Look for the following papers:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC394510/pdf/emboj00041-0155.pdf
https://www.ncbi.nlm.nih.gov/pubmed/11521719
https://www.ncbi.nlm.nih.gov/pubmed/24706169
http://www.nature.com/onc/journal/v19/n53/full/1203967a.html
https://cdn.intechopen.com/pdfs-wm/42312.pdf
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021475/
Mainly, HER family receptors prefer heterodimerization over homodimerization. For example, when there is HER2 overexpression, only then homodimerization occurs. HER family receptors, form heterodimers with their own family members. Apart from this, HER2 cross talk is a well-recognized feature in breast cancerthat leads to resistance towards anti-HER2 agents. HER2 can also form heterodimers with other family receptors those having similar homology to HER2, such as IGF1R.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3021475/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3060045/
EGF. TGF-α, epigen, epiregulin, neuregulin 1-4
- Badges
- Science topic
- Similar topics
- Medicine
- Oncology
- Cancer Research