p53 mutations & temozolomide
4601 patiens have been pretreated with temozolomide, chemeo and surgiry.
p53 could be problematic for 4601.
However, Temozolomide seems to be able to kill wild type p53, which 4601 has no data on.
Therefore, tested population potentially problematic for 4601 is addressed by TMZ.
By shutting down AKT, mutated p53 should activate cell death.
https://mct.aacrjournals.org/cgi/content/full/5/9/2182
Resistance to temozolomide also involves p53 status, Chk1- andChk2-mediated G2 checkpoint pathways, and Akt activation. Inresponse to temozolomide, p53 induces cell cycle arrest andapoptosis (4). On the other hand, MGMT inactivation may facilitateAT-GC mutations on p53 (23, 24), explaining the correlationbetween MGMT inactivation and p53 dysfunction (25, 26). In responseto temozolomide, Chk1 induces G2 arrest preventing from celldeath independently of p53 status (5). Akt pathway activation,which is a frequent feature in glioblastoma, bypasses thesemechanisms, preventing both G2 arrest and cell death (6). Again,none of the genes differentially expressed in our microarrayanalysis involved these pathways.