ERBB2andKRASAlterations Mediate Response to EGFR Inhibitors in early stage Gallbladder Cancer

Abstract

The uncommonness of gallbladder cancer has contributed to the generally poor understanding of the disease, with scant reports restricted to advance-stage tumors. Here, using an integrated analysis of whole exome and phospho-proteome, we show recurrent activating ERBB2 and KRAS somatic mutations are present in 6 and 3 of 44 early-stage rare gallbladder tumors, respectively. In vitro and in vivo cell-based and biochemical assays reveal an essential role of ErbB pathway activation for the survival of gallbladder cells. Interestingly, the genetic and pharmacological dependencies of gallbladder cells are dependent on the KRAS mutant allele status, reminiscent of the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer. In overall, we present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, leading to an early adoption of an approved treatment regimen for gallbladder cancer patients.

Raman spectroscopy‐based detection of RNA viruses in saliva: A preliminary report

“…The following day, transfection of GFP-tagged lentiviral vector, pLL3.7 along with the packaging plasmids pPAX and pVSVG in 2:1:0.5 ratio using lipofectamine 3000 was performed according to manufacturer's instructions. The viral supernatant was collected 48-and 72-hours post-transfection, filtered using 0.45-μ filter and subjected to ultracentrifugation at 30 000 rpm for 90 minutes at 4 C. The pellet was resuspended in 1 mL serum-free Dulbecco's Modified Eagle's medium (DMEM) media [15].…”

“…The next day, transduction of the viral particles were performed using two dilutions (1:10; 1:1000) in plain DMEM using 8 μg/mL polybrene in HEK293FT cells. GFP-positive cells were observed 48 hours post-transduction [15].…”