NorthWest Biotherapeutics Inc (NWBO)

[abeta]

doc -

I'm downstream of that ......

I'm at -

PTEN loss is extremely frequent in GBM (40%) and correlates with TMZ resistance

Context

Glioblastoma multiforme (GBM) is the most malignant form of glioma with a 5-year survival rate of 5% [150]. Besides surgery, the current therapeutic regimen is based on radiotherapy and temozolomide (TMZ) administration. PTEN loss is extremely frequent in GBM (40%) and correlates with TMZ resistance [200]. Consistently, treatment with TMZ doubles the fraction of stem-like SP cells, thus enhancing their tumorigenic potential. Inhibition of PI3K/AKT pathway with a specific inhibitor (LY294002) has been proposed to reduce multi-drug resistance mediated by ABCG2 in cancer stem-like cells and improve GBM chemosensitivity [74].

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721423/

This is more round about -

Importantly, ABT-888 does enhance TMZ efficacy in Pten deficient glioblastoma allografts and spontaneous tumors, even in Abcb1/Abcg2 proficient wild-type mice. Loss of PTEN occurs frequently in glioblastoma (36%) and in silico analysis on patient with glioblastoma samples revealed that it is associated with a worse overall survival (310 days vs. 620 days, n = 117).

CONCLUSIONS:
The potential of ABT-888 in glioblastoma can best be demonstrated in patients with PTEN null tumors. Therefore, clinical trials with ABT-888 should evaluate these patients as a separate group. Importantly, inhibition of ABCB1 and ABCG2 (by elacridar) may improve the efficacy of TMZ/ABT-888 therapy in all glioblastoma patients.

https://www.ncbi.nlm.nih.gov/pubmed/24647572

I'm at -

a) We have a ALOT of mMGMT ALIVE at 36 months.
b) their on TMZ and VAX
c) GBM comes in 4 or 5 silos - ignoring the newer 2019 articles
d) dumbing c) down to MES and Classical
e) DNA methylation lives in 6 clusters
f) the important ones from our perspective are C1 and C3
g) C3 = uMGMT (unmethylated) - we appear effective don't know why
NF1 ? P53 wild? beats me

h) C1 cluster (DNA methylation) = mMGMT
i) TMZ resistance kicks in due to PTEN
j) VAX has an effect on PTEN - extending TMZ effective

Is the above correct. Not a chance .... but its all I got.
And - to me - it hangs together.

EDIT - are ALL those 10 yr ALIVE people on VAX -ALSO- on SOC?

OR - TMZ

regards