Differential compensation mechanisms define resistance to PI3K inhibitors in PIK3CA amplified HNSCC.

ABSTRACT:

Objective

Recent sequencing studies of head and neck squamous cell carcinomas (HNSCCs) have identified the phosphatidylinositol 3-kinase (PI3K) pathway as the most frequently mutated, oncogenic pathway in this cancer type. Despite the frequency of activating genomic alterations in PIK3CA (the gene encoding the catalytic subunit of PI3K, targeted inhibitors of PI3K have not shown clinical efficacy as monotherapies. We hypothesized that co-dependent pathways, including the Ras-MEK-ERK pathway, may still be functional in the presence of PI3K inhibitors and might serve as mediators of this resistance.

Methods

We assessed the hypothesis using resazurin cell viability and trypan blue exclusion assays. We also used Western blot to characterize Ras-MEK-ERK pathway activity.

Study

SUBMITTER: Michmerhuizen NL 

PROVIDER: S-EPMC5167357 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature