Pancreatic Cancer: The Silent Killer
It is estimated that there are over 338,000 new cases of pancreatic cancer worldwide. in 2012, 331,000 people died from pancreatic cancer. Because the therapies for other cancers have been showing more advancement the researchers feel that pancreatic cancer is liable to become the second leading cause of cancer death worldwide. Patients with advanced pancreatic cancer, to survive more than a year is only slightly improved due to use of systemic chemotherapy and the combining use of other chemotherapies already available. This trial that adjuvant therapy using gemcitabine is the standard of care based on similar survival to and less toxicity than paired with 5-fluorouracil/folinic acid in patients with resected pancreatic cancer (meaning they have had all or part of the tumor removed surgically). In addition, other trials have shown better survival and tumor response with gemcitabine and capecitabine as opposed to gemcitabine used alone in advanced or metastatic pancreatic cancer. The outcome of the study found promise with the use of gemcitabine and capecitabine resulting in an increase in survival times to between two and five years without relapse (Neoptolemos et al, 2017)
Pancreatic cancer is a lethal malignancy that lacks specific diagnostic markers. Poor survival for pancreatic cancer stems from late diagnosis, asymptomatic early stages, high chemotherapy resistance, and rapid metastatic progression. The ability to diagnose pancreatic cancer in asymptomatic patients is expected to allow a greater number of patients to undergo potentially curative resection and greatly improve their prognosis.
Attempting to find effective biomarkers for the early diagnosis of pancreatic cancer is an ongoing endeavor. A minimally invasive early diagnostic test that has high sensitivity and specificity and is capable of distinguishing pancreatic cancer at an operative stage from benign disease is highly desirable. Notable MUC5AC is undetectable in the normal pancreas, cancer adjacent normal pancreas, and the chronically inflamed pancreas but exhibits differential expression in cases pancreatic cancer.
Biliary obstruction is one of the major confounding factors for accurate detection of pancreatic cancer. The familial group with a history of pancreatic cancer showed some individuals that had visible levels of MUC5AC but as of this article, no follow-up information to determine if any of them ended up with malignancy. There is much promise of MUC5AC that future assessment is warranted.
It has the potential to monitor patient responses post-treatment. As such it will be of immediate interest to evaluate the performance of MUC5AC in combination with CA19-9 in a cohort of pancreatic cancer patients. Early detection is important as an early diagnosis for the best possible outcomes from treatment. In addition, early-stage surgery adds to the best curative response. The study has high hopes for the combination of MUC5AC and CA19-9 in finding biomarkers that can help improve the current five-year survival rate from less than six to 20% in the near future (Kaur et al, 2017).
A diagnosis of pancreatic cancer is devastating owing to its poor prognosis, with a five-year survival rate of 9%. Currently, most individuals are diagnosed at a late stage when treatment options are limited. Early detection of pancreatic cancer provides the greatest hope for making substantial improvements in survival. This report was published from a recent forum held in Boston. The purpose was to discuss initiatives of various research institutions to make pancreatic cancer more easily detectable in early stages and more treatable.
Pancreatic cancer is an uncommon but deadly cancer. Its high mortality makes it the third leading cause of cancer-related death in the US. It is only major cancer with a rising mortality rate as well. It is characterized by a late onset of symptoms rapid progression and death. At present no clinically useful testing exists to identify early pancreatic cancer. So far the only identified at-risk group that has been found is among those who are newly diagnosed as diabetic.
Approximately 20% to 25% of people with pancreatic cancer develop diabetes within six to 36 months before the diagnosis of pancreatic cancer. The end goal of this forum is to develop an effective protocol for early detection of pancreatic cancer that can be used at primary care level in healthcare systems. Patients with pancreatic cancer need data-driven tools to identify their disease earlier and to personalize treatment decisions.
Researchers have emphasized that cancer is more than just a tumor. The most substantial biomarkers may be from the environment around the cancer and that information must be captured. The enthusiastic support of the cause shown at the forum was encouraging to see and bodes well for the successful emergence of a strategy for early detection in the near future (Kenner et al, 2017).
The incident of pancreatic ductal adenocarcinoma (PDAC) is increasing. Projections show that it will surpass breast cancer to become the second-leading cause of cancer-related death by 2030 serves as a wakeup call to stakeholders including researchers and healthcare systems. Earlier detection and diagnosis is one factor that could alter this trajectory. Researchers have made substantial efforts to identify biomarkers that can assist in diagnosis pancreatic cancer at a stage where it can be successfully treated.
Pancreatic cancer, however, is a disease with great inter-individual variations. This means researchers need larger groups for a study to ensure adequate representation of subtypes. Therefore, in order to acquire sufficient samples of patients with cancer and control individuals for biomarker studies multicenter collaborations are needed. Metabolomics-the study of metabolites related to specific cellular processes is emerging as a means of detecting disease-induced alterations in metabolism. A global study was able to locate identified the metabolites that distinguished pancreatic ductal adenocarcinoma from chronic pancreatitis.
The biomarker signature incurred fewer false positives and detected more true positives than from previous methods. In summary, the authors recruited patients from three centers to achieve a unique large patient study. This group then was extensively studied for metabolic analysis and it led to a validation of the biomarker signature that accurately discriminates between pancreatic ductal adenocarcinoma from chronic pancreatitis. This study uncovered potential metabolites for the diagnosis of pancreatic ductal adenocarcinoma and indeed for cancer diagnosis in general (Costello, 2018).
Pancreatic ductal adenocarcinoma (PDAC) is a lethal form of cancer with less than 7% of patients surviving past five years. This study endeavored to identify T cell antigen in long-term survivors. By investigating the specific neoantigen qualities promoting T cell activation in long-term survivors they found that long-term survivors were enriched in neoantigen qualities defined by a fitness model. This neoantigen quality can now be used as a biomarker for immunogenic tumors that may assist in the application of immunotherapies in the future.
Recent data has shown T cell-recognized neoantigens can be selectively lost from the tumor cell population either by mutant loss or overall reduced gene expression. This study shed insight into the immunobiology of pancreatic ductal adenocarcinoma, a presumed poorly immunogenic and checkpoint blockade refractory tumor, demonstrating that neoantigens may be T cell targets in long-term survivors. Overall survival and patient overlap of short and long-term survivors in the tissue microarray. Although the propensity to generate neoantigens maybe related to their large size the study didn’t detect trends toward neoantigen formation based on gene size done across cohorts or pipelines. Because the cohort used in this study validation must be sought in a larger study (Balachandran et al, 2017).
Balachandran, V.P. et al. (2017). Identification of unique neoantigen qualities in long term pancreatic cancer survivers. Nature,551(7681).
Costello, E. (2018). Metabolomics-based biomarker signature discriminates pancreatic cancer from chronic pancreatitis. BMJJournals: Gut,67(1).
Kaur, S. et al. (2017). A combination of MUC5AC and CA19-9 improves the diagnosis of pancreatic cancer: A multicenter study. American Journal of Gastroenterology,112(1).
Kenner, B.J. et al. (2017). Early detection of pancreatic cancer: The role of industry in the development of biomarkers. Pancreas, 46(10).
Neoptolemos, J.P. et al. (2017). Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicenter, open-label, randomized Phase 3 trial. The Lancet,389(10073).