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Unique clinical trial helps researchers gain new molecular insight on advanced disease.
Posted On: March 02, 2020
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Pancreatic cancer affects the pancreas (illustrated above), an organ in the abdomen that produces hormones, such as insulin, to help maintain blood sugar within a healthy range.
Despite advanced pancreatic cancer being the most commonly diagnosed form of the disease, little is known about its genetic and molecular features.
“Most molecular studies on pancreatic cancer have examined early stage disease, which is found in a minority of the patient population. This is mostly due to difficulty in obtaining sufficient tumour tissue for research from patients with advanced disease,” says Dr. Faiyaz Notta, a Scientist at Princess Margaret (PM) Cancer Centre.
To address this, a unique clinical trial known as COMPASS was launched by Dr. Jennifer Knox, a Medical Oncologist at PM Cancer Centre. The trial enrolled patients with advanced pancreatic cancer and aimed to comprehensively characterize the genetic content of their tumours.
Dr. Notta and Dr. Steve Gallinger, a Surgical Oncologist at PM Cancer Centre, examined pancreatic tumours collected from 314 patients, including 111 with advanced disease from the COMPASS trial.
The researchers found that the pancreatic cancers could be grouped into five different subtypes based on their genetic information. One subtype, referred to as Basal-like-A, was mainly found in advanced disease. Prior to this, only two subtypes of pancreatic cancer had been described. The study’s findings also indicate that the disease subtypes likely emerged from specific genetic alterations during disease development.
These findings help to explain why patients with pancreatic cancer display a wide range of responses to the same anti-cancer drug. In addition, they will guide the design of new strategies that are targeted to each subtype of advanced disease.
This work was supported by the Government of Ontario, the Ontario Institute for Cancer Research, The Princess Margaret Cancer Foundation, the Terry Fox Research Institute, the Canadian Cancer Society and the Pancreatic Cancer Canada Foundation.
Chan-Seng-Yue M, Kim JC, Wilson GW, Ng K, Figueroa EF, O'Kane GM, Connor AA, Denroche RE, Grant RC, McLeod J, Wilson JM, Jang GH, Zhang A, Liang SB, Borgida A, Chadwick D, Kalimuthu S, Lungu I, Bartlett JMS, Krzyzanowski PM, Sandhu V, Tiriac H, Froeling FEM, Karasinska JM, Topham JT, Renouf DJ, Schaeffer DF, Jones SJM, Marra MA, Laskin J, Chetty R, Stein LD, Zogopoulos G, Haibe-Kains B, Campbell PJ, Tuveson DA, Knox JJ, Fischer SE, Gallinger S, Notta F. Transcription phenotypes of pancreatic cancer are driven by genomic events during tumor evolution. Nat Genet. 2020 Feb 12. doi:
10.1038/s41588-020-0588-3.