Abdullah A. Osman

TL;DR: It is shown that GOF mutp53s inhibit AMP-activated protein kinase (AMPK) signaling in head and neck cancer cells, and direct inhibition of AMPK activation is an important mechanism through which mut p53s can gain oncogenic function.

TL;DR: An adrenergic differentiation signature is identified by comparing the transcriptomes of cancer-associated trigeminal sensory neurons with those of endogenous neurons in mouse models of oral cancer to show that loss of TP53 leads to adrenergic transdifferentiation of tumour-associated sensory nerves through loss of the microRNA miR-34a.

TL;DR: An association between the presence of high-risk mutations and decreased expression of TP53 target genes is documented, highlighting key cellular pathways that are likely to be dysregulated by this subset of p53 mutations that confer particularly aggressive tumor behavior.

TL;DR: Results indicate that HNSCC cells expressing high-risk p53 mutations are significantly sensitized to cisplatin therapy by the selective wee-1 kinase inhibitor, supporting the clinical evaluation of MK-1775 in combination with cisPlatin for the treatment of patients with TP53 mutant H NSCC.

TL;DR: This is the first report showing the ability of a Chk kinase inhibitor to sensitize TP53-deficient HNSCC to cisplatin in a synthetic lethal manner, which has significance given the frequency of TP53 mutations in this disease and because cis platin has become part of standard therapy for aggressive H NSCC tumors.