Modeling Therapy Response and Spatial Tissue Distribution of Erlotinib in Pancreatic Cancer

Molecular Cancer Therapeutics
Barbara M GrünerJens T Siveke

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is likely the most aggressive and therapy-resistant of all cancers. The aim of this study was to investigate the emerging technology of matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) as a powerful tool to study drug delivery and spatial tissue distribution in PDAC. We utilized an established genetically engineered mouse model of spontaneous PDAC to examine the distribution of the small-molecule inhibitor erlotinib in healthy pancreas and PDAC. MALDI IMS was utilized on sections of single-dose or long-term-treated mice to measure drug tissue distribution. Histologic and statistical analyses were performed to correlate morphology, drug distribution, and survival. We found that erlotinib levels were significantly lower in PDAC compared with healthy tissue (P = 0.0078). Survival of long-term-treated mice did not correlate with overall levels of erlotinib or with overall histologic tumor grade but did correlate both with the percentage of atypical glands in the cancer (P = 0.021, rs = 0.59) and the level of erlotinib in those atypical glands (P = 0.019, rs = 0.60). The results of this pilot study present MALDI IMS as a reliable technology to study drug delive...Continue Reading

References

Dec 3, 2002·Nature Reviews. Cancer·Nabeel Bardeesy, Ronald A DePinho
Dec 31, 2005·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Jie LingChandra Prakash
Apr 6, 2006·Proceedings of the National Academy of Sciences of the United States of America·Nabeel BardeesyRonald A Depinho
Jul 25, 2006·Nature Reviews. Cancer·Andrew I Minchinton, Ian F Tannock
Sep 15, 2006·Analytical Chemistry·Sheerin Khatib-ShahidiRichard M Caprioli
Apr 25, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Malcolm J MooreUNKNOWN National Cancer Institute of Canada Clinical Trials Group
May 31, 2007·Journal of Mass Spectrometry : JMS·Luca SignorGérard Hopfgartner
Sep 11, 2007·Journal of the American Society for Mass Spectrometry·Markus StoeckliDieter Seebach
Sep 27, 2007·Journal of the National Cancer Institute·Olivier TrédanIan F Tannock
Jun 18, 2009·Journal of Cancer Research and Clinical Oncology·Beata ZahorowskaJia-Lin Yang
Apr 30, 2010·The New England Journal of Medicine·Manuel Hidalgo
Mar 29, 2011·Journal of Proteomics·György Marko-VargaAkos Végvári
Nov 15, 2011·Bioanalysis·Stephen CastellinoDavid Wagner
Sep 15, 2012·Cancer Cell·Christine M ArditoJens T Siveke
Sep 13, 2013·Analytical Chemistry·M Reid Groseclose, Stephen Castellino
Oct 19, 2013·Journal of Proteome Research·Ákos VégváriGyörgy Marko-Varga

❮ Previous
Next ❯

Citations

Sep 20, 2018·Scientific Reports·Shin-Heng ChiouBarbara M Grüner
Mar 31, 2021·Clinical and Translational Medicine·An-Dong LiuXuan Cao
Jul 26, 2017·Talanta·María Ramos-PayánMiguel Ángel Bello-López

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.