Pancreatic Cancer Research
These clinical features notwithstanding, efficacious therapeutic options do not exist and less than 10% of patients respond meaningfully to standard of care (Gemcitabine). While some progress developing combination therapies has been achieved in the past few years, these are all still toxic chemotherapy-based regimes that are difficult to tolerate and extend median survival marginally. More to the point, targeted therapies – those that avoid harmful side-effects of chemotherapy and provide a majority of patients with meaningful and durable response – are completely absent in the therapeutic arsenal available for pancreatic cancer. Given this information, it has become resoundingly clear that a strategy not altogether the same as that applied successfully in other solid tumors is going to be required to develop effective treatment options for patients with pancreatic cancer. As such, our research focuses on the unique metabolic nature of pancreatic tumors and is aimed at defining and exploiting metabolic vulnerabilities in search of new, selective drug targets (Lyssiotis, Cantley. Clin Cancer Res 2014).
In addition to the clinical trial being initiated at MD Anderson, we are now also developing a program to examine glutamine addiction. Namely, in collaboration with the Kimmelman and Lairson labs and through funding from the Lustgarten Foundation, we have run drug screens on >2Mi molecules against two pancreatic cancer metabolism targets and are now validating lead candidates. In the near future, their activity will be assessed in animal models of pancreatic cancer in combination with currently available therapeutic modalities. Highly promising methods will be developed for clinical application, as is being done with our inhibitors of mitochondrial metabolism. Ultimately, it is our hope that these new understandings in pancreatic tumor metabolism will bring about better therapeutic options for this dreaded disease.
Viale A, Pettazzoni P, Lyssiotis CA, Ying H, Sanchez N, Marchesini M, Carugo A, Green T, Seth S, Giuliani V, Kost-Alimova M, Muller F, Colla S, Nezi L, Genovese G, Deem AK, Kapoor A, Carugo A, Yao W, Brunetto E, Kang Y, Yuan M, Asara JM, Wang YA, Heffernan TP, Kimmelman AC, Wang H, Fleming J, Cantley LC, DePinho R & Draetta G. Nature (2014) 30, 628–632.
Abstract | PDF | Extended Figures | Times cited: 252
Glutamine Supports Pancreatic Cancer Growth Through a KRAS-Regulated Metabolic Pathway
*Son J, *Lyssiotis CA [*co-lead authors], Ying H, Wang X, Hua S, Ligorio M, Perera RM, Ferrone CR, Mullarky E, Shyh-Chang N, Kang Y, Fleming JB, Bardeesy N, Asara JM, Haigis MC, DePinho RA, Cantley LC & Kimmelman AC. Nature (2013) 496, 101–105.
Abstract | PDF | Supporting Information | Times cited: 506
Oncogenic Kras Maintains Pancreatic Tumors through Regulation of Anabolic Glucose Metabolism
*Ying H, *Kimmelman AC, *Lyssiotis CA [*co-lead authors], Hua S, Chu GC, Fletcher-Sananikone E, Locasale JW, Son J, Zhang H, Coloff JL, Yan H, Wang W, Chen S, Viale A, Zheng H, Paik J, Lim C, Guimaraes AR, Martin ES, Chang J, Hezel AF, Perry SR, Hu J, Gan B, Xiao Y, Asara JM, Weissleder R, Wang YA, Chin L, Cantley LC & DePinho RA. Cell (2012) 149, 656–670.
Abstract | PDF | Supporting Information | Times cited: 592