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“Pancreatic cancer remains the most fatal human tumor type. The aggressive tumor biology coupled with the lack of early detection strategies and effective treatment are major reasons for the poor survival rate.
Collaborative research efforts have been devoted to understand pancreatic cancer at the molecular level. Large-scale genomic studies have generated important insights into the genetic drivers of pancreatic cancer.
In the post-genomic era, protein sequencing of tumor tissue, cell lines, pancreatic juice, and blood from patients with pancreatic cancer has provided a fundament for the development of new diagnostic and prognostic biomarkers.
The integration of mass spectrometry and genomic sequencing strategies may help characterize protein identities and post-translational modifications that relate to a specific mutation. Consequently, proteomic and genomic techniques have become a compulsory requirement in modern medicine and health care.
These types of proteogenomic studies may usher in a new era of precision diagnostics and treatment in patients with pancreatic cancer.
“Integrated genomic analysis of 456 pancreatic ductal adenocarcinomas identified 32 recurrently mutated genes that aggregate into 10 pathways: KRAS, TGF-β, WNT, NOTCH, ROBO/SLIT signalling, G1/S transition, SWI-SNF, chromatin modification, DNA repair and RNA processing…
These data infer differences in the molecular evolution of pancreatic cancer subtypes and identify opportunities for therapeutic development…”
“Treatment based on genomic profiling, also known as precision medicine, may hold the promise of improved outcomes for a subset of patients with pancreatic cancer. Pancreatic cancer is the third leading cause of cancer deaths in the United States and with a survival rate of just 8% current treatments are largely ineffective. Genomic profiling, according to a pair of recent studies published by researchers at the University of Pittsburgh and the University of Pittsburgh Medical Center (UPMC) may be the key to more effective pancreatic cancer treatment.
The first study investigated genomic changes in 100 patients with gastrointestinal cancer including colorectal and pancreatic cancers. Common mutations in each cancer were identified and recommendations could be made for 38% of patients. However, due to rapid disease progression, only 14% of patients could follow the recommended treatment. Half of the patients following genome-informed therapy treatment showed improved overall survival. One patient had a mutation in the ALK gene, a gene that is commonly implicated in other forms of cancer including breast, colon, and lung for which current drug treatments have been successful.1
The second study investigated the genomic profile of more than 3000 patients with pancreatic cancer. Only 5 patients (0.2%) had mutations in ALK. Four of the 5 patients were treated with commonly used ALK inhibiting drugs. Positive effects including disease stability, tumor shrinkage, and lower levels of a pancreatic specific biomarker were observed in 3 patients.2
“Together, these 2 findings begin to capture the promise of precision medicine in pancreatic cancer, which has so far not experienced the same success with targeted treatments as other cancer types…,”