Abstract
The irreversible ERBB1/2/4 inhibitor neratinib has been shown in vitro to rapidly reduce the expression of ERBB1/2/4 and RAS proteins via autophagic/lysosomal degradation. We have recently demonstrated that neratinib and valproate interact to suppress the growth of 4T1 mammary tumors but had not defined whether the [neratinib + valproate] drug combination, in a mouse, had altered the biology of the 4T1 cells. Exposure of 4T1 mammary tumors to [neratinib + valproate] for three days resulted, two weeks later, in tumors that expressed less ERBB1, K-RAS, N-RAS, indoleamine-pyrrole 2,3-dioxygenase (IDO-1), ornithine decarboxylase (ODC) and had increased Class I MHCA expression. Tumors previously exposed to [neratinib + valproate] grew more slowly than those exposed to vehicle control and contained more CD8+ cells and activated NK cells. M1 but not M2 macrophage infiltration was significantly enhanced by the drug combination. In vitro exposure of 4T1 tumor cells to [neratinib + valproate] variably reduced the expression of histone deacetylases 1-11. In vivo, prior exposure of tumors to [neratinib + valproate] permanently reduced the expression of HDACs 1-3, 6 and 10. Combined knock down of HDACs 1/2/3 or of 3/10 rapidly reduced the e...Continue Reading
References
Sep 23, 2014·Trends in Pharmacological Sciences·Oliver H KrämerAndreas Sellmer
Mar 5, 2016·Oncotarget·Laurence BoothPaul Dent
Oct 25, 2016·Cancer Letters·Yingqiu ZhangHan Liu
Dec 3, 2016·Oncotarget·Laurence BoothPaul Dent
Feb 2, 2017·Oncotarget·Laurence BoothPaul Dent
Nov 16, 2017·Oncotarget·Laurence BoothPaul Dent
Nov 23, 2017·Oncotarget·Laurence BoothPaul Dent
Dec 9, 2017·Cancer Biology & Therapy·Laurence BoothPaul Dent
Citations
Feb 7, 2018·Cancer Biology & Therapy·Laurence BoothPaul Dent
Aug 25, 2018·Cancer Biology & Therapy·Laurence BoothPaul Dent
Sep 6, 2018·Cancer Biology & Therapy·Laurence BoothPaul Dent
Jun 21, 2018·Cancer Biology & Therapy·Laurence BoothPaul Dent
Dec 21, 2018·Cancer Biology & Therapy·Laurence BoothPaul Dent
Jun 30, 2019·Oncogene·Paul DentJohn F Hancock
Jan 9, 2020·Journal of Cellular Physiology·Paul DentJohn F Hancock
Feb 13, 2020·Frontiers in Oncology·Paul DentJohn F Hancock
Jan 16, 2018·Cancer Biology & Therapy·Laurence BoothPaul Dent
Dec 31, 2019·Immunometabolism·Paul DentAndrew Poklepovic
Sep 12, 2018·Journal of Cellular Physiology·Laurence BoothPaul Dent
Sep 15, 2019·Cellular Signalling·Paul DentJohn F Hancock
Jul 13, 2021·Aging·Paul DentEric M Reiman
Jan 9, 2020·Cellular Signalling·Paul DentJohn F Hancock