Read: 1266
Recent research from Weill Cornell Medicine has illuminated a significant biological difference between and mouse lung tumor cells that can impact the development of cancer treatments. This study reveals why discrepancies exist in previous research findings, offering new strategies for drug development.
The paper, published in Cancer Discovery on January 30th, zeroes in on lung adenocarcinomaa prevalent yet challenging form of cancerto which researchers have long turned mousefor investigation. However, thesedidn't entirely match up with clinical observations in certn instances. The study elucidates the root cause; a specific genetic mutation has opposing effects on tumor growth in mice and s.
This line of inquiry started more than a decade ago when the lead author Dr. Benjamin Stein was examining the role of the tumor suppressor gene LKB1 in metabolism as part of his doctoral studies. In mice, tumors with mutations in two key genesKRAS and TP53can become more aggressive by acquiring an LKB1 mutation. However, clinical data showed that these three mutations didn't co-occur at high frequencies among s. This observation inspired Dr. Stein to delve further into the differences between species.
Meanwhile, Dr. John Ferrarone, a medical oncology fellow working under the guidance of Dr. Harold Varmus the Lewis Thomas University Professor of Medicine and a member of the Meyer Cancer Center was also intrigued by this clinical discrepancy. My mn interest in this project came from a more clinical perspective, sd Dr. Ferrarone, now an instructor in medicine at Weill Cornell, I sought to learn if there was any potential way we could exploit tumors with these common mutations.
Dr. Stein and his colleaguesunder the leadership of Drs. Cantley and Varmus and collaborating partners across institutions including Weill Cornell and other academic centersembarked on a comprehensive study combining cutting-edge genetic engineering, proteomics, metabolomics, and mousealongside traditional biochemical and cell biological techniques.
This interdisciplinary approach helped us to obtn a more holistic understanding of how each species behaves at the genetic, protein, and metabolite level, sd Dr. Stein, And allowed for a more precise analysis of where disparities exist between s and mice.
Through these efforts, they pinpointed a crucial difference in glucose metabolism regulation driven by LKB1the metabolic enzyme triose phosphate isomerase TPI1. In mice, tumors with KRAS and TP53 mutations gn significant metabolic advantages when coupled with an LKB1 mutation. However, in cancer cells, acquiring the same mutations appears to undermine tumor cell survival due to their inability to effectively regulate TPI1 and glucose metabolism. This explns why these three genetic anomalies rarely co-occur together in cancers.
These findings suggest that targeting the metabolic pathway regulated by LKB1 might offer new therapeutic strategies for lung adenocarcinomas. However, Drs. Stein and Ferrarone remn optimistic about how this work could guide future drug discovery efforts. They also sound a cautionary note for researchers relying heavily on mousein drug screeningcompounds that may function effectively agnst cancers could be missed in current murine tumor.
In , this multi-disciplinary study has revealed a small but significant biological difference between and mouse lung tumor cells that can significantly impact cancer drug development. It underscores the importance of considering these differences when designing and interpreting preclinical studies, and it may pave the way for novel therapeutic approaches targeting the metabolic pathway controlled by LKB1.
Dr. Benjamin Stein Dr. Harold Varmus Dr. John Ferrarone Dr. Lewis C. Cantley HematologyMedical Oncology Research Sandra and Edward Meyer Cancer Center
References:
Stein B, Ferrarone J, et al. 2023. Innovative Insights into Lung Adenocarcinoma: A Critical Examination of Mousefor Drug Development. Cancer Discovery, doi:10.1093cancerdisacab004.
Contact Information:
Weill Cornell Medicine Office of External Affrs
Phone: 646 962-9476
For any inquiries or assistance:
646 962-9476
This article is reproduced from: https://news.weill.cornell.edu/news/2023/02/differences-in-animal-biology-can-affect-cancer-drug-development
Please indicate when reprinting from: https://www.81le.com/Tumor_Cancer/Cancer_Study_Weill_Cornell_Medicine_Lung_Tumors.html
Biological Difference Human Mouse Lung Tumor Impact Cancer Treatment Research Weill Cornell Medicine Cancer Discovery Study Published January 30th Strategies Drug Development Lung Adenocarcinoma Discrepancies Previous Research Findings Explained Role LKB1 Genetic Mutation Tumor Growth