Guest Editors
Marya Kozinova
Fox Chase Cancer Center
Dr.Marya Kozinova graduated in biophysics and medicine from the Russian National Research Medical University (RNRMU, Russia) in 2014. Afterward, she moved to the United States, where she performed research in cancer biology and earned her PhD from the joint graduate program between RNRMU and the Fox Chase Cancer Center (FCCC). During her PhD training at Dr.Lori Rink's laboratory, Marya studied the mechanisms behind resistance to small-molecule kinase inhibitors and evaluated new therapeutic targets in preclinical models of Gastrointestinal Stromal Tumors. Thereafter, Marya aimed to combine her knowledge of signaling and translational cancer research with the fascinating field of bioinformatics and data analysis. Thus, she joined the group of Dr.Phil Abbosh in FCCC, where she presently works as a Scientific Associate. Marya’s research explores genomic and transcriptomic changes that occur in kidney and bladder cancers to identify potential avenues for personalized treatment strategies in these malignancies with a special focus on Immuno-oncology.
Faryal Ijaz
Hiroshima University
Dr. Faryal Ijaz earned her PhD. in Medical Sciences from the Hamamatsu University School of Medicine, Japan, where she investigated the role of tubulin tyrosine ligases in maintaining the structure of plasma membrane. After completing her doctorate, she moved to the USA to pursue her postdoctoral in Cell Biology at the Houston Methodist Research Institute, Texas. As a postdoctoral fellow, she helped identify the molecular pathways involved in the development of atherosclerosis in radio-resistant endothelial stromal cells. Currently, she is an Assistant Professor at the Department of Anatomy and Developmental Biology, Hiroshima University, Japan, studying the physiological and pathophysiological role of extracellular vesicles and their interaction with the cellular microenvironment.
Renuka Raman
Weill Cornell Medical College
Dr. Renuka Raman earned her PhD in Cell Biology from the Tata Institute of Fundamental Research, India where she studied the role of polarity proteins in the regulation of dynamic actin-based structures known as micro ridges. This was the first report demonstrating a mechanism for the molecular regulation of micro ridges invertebrates. She then moved to the USA in 2017 to pursue post-doctoral research in cancer biology at the Icahn School of Medicine at Mount Sinai, where she contributed to the identification of a novel radiation response pathway involving IRAK1 kinase and was the recipient of the ‘National Cancer Center Postdoctoral Fellowship’. She continued her training at Weill Cornell Medical College, where she generated patient-specific models of RET rearranged thyroid cancer and currently identifies novel molecular targets to overcome resistance to receptor tyrosine kinase inhibitors in lung and thyroid cancers.
Malvika Pompaiah
University Medical Center, CBU
Dr. Malvika Pompaiah received her PhD in Molecular Biology from the Max Planck Institute for Infection Biology, Germany where she investigated the pathogenic role of Helicobacter pylori (Hp) in gastric cancer. She continued her post-doctoral research on oncogenic protein, IQGAP1 and its new mechanisms in apoptosis. Next, she joined as a post-doctoral researcher at IMIB, Germany, where she employed patient-derived organoids (PDO) and single cell RNA technology and characterized new factors involved in Hp pathogenesis. Malvika pursued her passion for oncology by joining as a post-doctoral scientist at CBU, University Medical Center, Germany. Here she successfully generated and optimized the pipeline of PDO living biobanks for lung, colon, and gastric tumors to perform drug screens and elucidate oncogenic signaling. Another major project was on target therapy and precision medicine of GIST to identify new drug targets using multi-omics and drug screens.
Collection Overview
Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal neoplasms of the digestive system. GIST arises from the interstitial cells of Cajal (ICC), also called the pacemaker cells of the gastrointestinal tract. The majority of GISTs harbor gain-of-function mutations in the receptor tyrosine kinases (RTK) KIT or PDGFRA.
Patients with GIST do not respond favorably to conventional chemotherapeutics. However, targeting the KIT receptor with imatinib mesylate (IM) yields high response rates and has been the first-line therapy for the past 20 years. Despite high initial response rates, many patients ultimately develop resistance to IM by acquiring secondary mutations in RTK and/or activation of by-pass signaling. To address IM resistance in GIST, additional RTK inhibitors have been developed and four received FDA approval. Despite this progress, resistance recurs through similar mechanisms. New therapeutic approaches that overcome resistance will require further investigation of the genomic, transcriptomic, and proteomic features of GIST, particularly kinase signaling, as well as tumor heterogeneity and the interaction with the stromal and immune microenvironments.
This Method Collection aims to provide original insights into emerging methods and approaches for investigating GIST. Here, we emphasize translational strategies involving animal and human models for new drug testing, multi-omics research, and GIST-microenvironment interaction studies. It also provides a platform to showcase soft tissue sarcoma techniques that could be applied to advance GIST research. These protocols will help expedite new strategies for targeting treatment-resistant GIST.
Articles
Abstracts
Combined model based on clinical and enhanced CT texture features for predicting the liver metastasis of high-risk gastrointestinal stromal tumors
Haitao Jiang*1
1Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)