Latest Research News on pancreatic cancer : Aug – 2020

Latest Research News on pancreatic cancer : Aug – 2020

Molecular targeting therapy for pancreatic cancer

Pancreatic carcinogenesis is driven by multiple genetic and epigenetic changes. The epidermal growth factor receptor (EGFR) and its downstream signaling pathways, Ras-Raf-MEK-ERK axis, play important roles in pancreatic cancer development. The phosphoinositol 3 kinase (PI3 K)/Akt and the nuclear factor κB (NF-κB) pathways control both proliferation and resistance to apoptosis of pancreatic cancer. The role of cyclooxygenase (COX) and lipoxygenase (LOX) in the development of pancreatic cancer has been made known recently. The elucidation of these molecular events has led to several distinct therapeutic advances, including therapies that target EGFR, the Ras-Raf-MEK-ERK axis, the COX-2 and LOX pathways, and others. Many novel agents have been developed and are undergoing clinical investigation, such as monoclonal antibodies against EGFR, tyrosine kinase inhibitors (TKIs), farnesyl transferase inhibitors (FTIs), Bay43-9006, CI-1040, CCI-779, celecoxib, and LY293111. This review highlights recent advances in the development of these agents. [1]

Borderline Resectable Pancreatic Cancer: Definitions, Management, and Role of Preoperative Therapy

With recent advances in pancreatic imaging and surgical techniques, a distinct subset of pancreatic tumors is emerging that blurs the distinction between resectable and locally advanced disease: tumors of “borderline resectability.” In our practice, patients with borderline-resectable pancreatic cancer include those whose tumors exhibit encasement of a short segment of the hepatic artery, without evidence of tumor extension to the celiac axis, that is amenable to resection and reconstruction; tumor abutment of the superior mesenteric artery involving <180° of the circumference of the artery; or short-segment occlusion of the superior mesenteric vein, portal vein, or their confluence with a suitable option available for vascular reconstruction because the veins are normal above and below the area of tumor involvement. With currently available surgical techniques, patients with borderline-resectable pancreatic head cancer are at high risk for a margin-positive resection. Therefore, our approach to these patients is to use preoperative systemic therapy and local-regional chemoradiation to maximize the potential for an R0 resection and to avoid R2 resections. In our experience, patients with favorable responses to preoperative therapy (radiographical evidence of tumor regression and improvement in serum tumor marker levels) are the subset of patients who have the best chance for an R0 resection and a favorable long-term outcome. [2]

Epidemiology of pancreatic cancer

In the United States the incidence of and mortality from pancreatic cancer have increased over the past several decades but have tended to level off in recent years. The rates are higher in blacks than in whites and higher in males than in females. Mortality rates increase with age but there appears to be a decline in elderly blacks, possibly on an artifactual basis. There is a suggestion that rates are higher in Jews. No consistent differences by socioeconomic status or by geographic location within the United States have been identified. Both genetic and environmental factors may be playing significant roles in this disease. Cigarette smoking may be etiologically related, or at the very least, may help to identify a group of patients at increased risk of pancreatic cancer. However, the relative risk estimated for cigarette smoking is much lower than that found for cancer of the lung. The leveling off in incidence and mortality rates for pancreatic cancer in recent years also differs from the time trends observed for lung cancer. However, this could result from differences in site-specific carcinogens and from the fact that the lung is the first organ to be exposed to cigarette smoke in the highest concentrations and prior to the metabolism of any of its components.

Dietary factors may have an important role in pancreatic cancer, but further research is needed to clarify this relationship. In particular, the possibility that dietary fats may be implicated and that vitamins or fiber may be protective in this disease remains to be explored. Finally, there is suggestive evidence that specific chemical exposures may be carcinogenic for the pancreas. Many of the data are from animal studies, and the findings from human studies are not entirely consistent. [3]

Identification of Candidate Biomarkers and Cancer Genes AHNAK2 and EPPK1 in Pancreatic Cancer

Aims: The lack of specific symptoms at early tumor stages, together with a high biological aggressiveness of the tumor contribute to the high mortality rate for pancreatic cancer (PC). Improved screening for earlier diagnosis, through the detection of diagnostic and prognostic biomarkers provides the best hope of increasing the rate of curatively resectable carcinomas. The aim of this study is to provide new targets for use as biomarkers in PC.

Study Design: In a previous study, we identified novel candidate cancer genes and biomarkers that were significantly upregulated in PC, through a meta-analysis of large number of microarray datasets, using bioinformatics methods.  In this study, we analyzed the expression of these genes in a panel of pancreatic cancer cell lines by quantitative Reverse Transcription-PCR (qRT-PCR).

Place and Duration of Study: Department of Chemistry and Biochemistry and Department of Biology, University of Northern Iowa, USA, between June 2014 and Dec 2015.

Methodology: We analyzed the expression of three genes, AHNAK2, EPPK1 and IGHG3 in a panel of seven standard PC cell lines, AsPC-1, BxPC-3, Capan-2, CFPAC-1, HPAF-II, PANC-1, and SW 1990 by Relative Quantification. qRT-PCR experiments were conducted in triplicate, and each experiment was replicated twice using different passages.

Results: AHNAK2 was significantly upregulated in all PC cell lines tested, with P values < 0.005 except for PANC-1 (P < 0.05). EPPK1 too was significantly upregulated (P < 0.05) in six of seven PC cell lines tested. While IGHG3 was nominally upregulated in all PC cell lines, upregulation was significant (P < 0.05) in only four PC cell lines.

Conclusion: Our results confirm that AHNAK2 and EPPK1 are novel candidates for use as biomarkers in pancreatic cancer. IGHG3 does not appear to be a suitable candidate, due to its low levels of expression in both PC and control cell lines. [4]

Exocrine Pancreatic Cancer: A Clinico-epidemiologic Study

Background: Incidence of pancreatic cancer is relatively low compared to other types of cancer but had the lowest survival rate of all cancers.

Objective: To describe clinical-epidemiological features of pancreatic cancer patients recorded in our region and assessed its different prognostic factors.

Materials and Methods: The medical records of patients with pancreatic cancer attended to Clinical Oncology, and Nuclear Medicine department and Oncology centre between 2005-2014 were reviewed.

Results: This retrospective study included 380 patients with exocrine pancreatic cancer. Median age was 56 years with male predominance (65%). The most predominant histologic type was adenocarcinoma with grade III in 55% of patients. Tumours were located at the head of the pancreas were 75.5%, followed by the body (20.8%). Most patients presented with metastatic disease (57.9%). The pain was the most common presenting symptom (63.9%), while jaundice was found in 47.4% of patients. 23.7% of patients were smokers and 19.7% suffered from diabetes mellitus. 1-year survival rate was 28%. On multivariate analysis; we found significant lower survival rate with male gender (P=0.004), high-grade disease (P=0.002), older age (P=0.001), PC located in tail and body (P=0.006), high level of CA19-9(> 37U/L) (P=0.001), and metastatic cases (P=0.003).

Conclusion: This study is a clinical-epidemiologic survey of pancreatic cancer in our locality. However, because of its relatively small number of patients and retrospective nature; larger prospective studies are needed to study the epidemiologic and genetic basis of pancreatic cancer in our region. [5]

Reference

[1] Xiong, H.Q., 2004. Molecular targeting therapy for pancreatic cancer. Cancer chemotherapy and pharmacology, 54(1), pp.S69-S77.

[2] Varadhachary, G.R., Tamm, E.P., Abbruzzese, J.L., Xiong, H.Q., Crane, C.H., Wang, H., Lee, J.E., Pisters, P.W., Evans, D.B. and Wolff, R.A., 2006. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Annals of surgical oncology, 13(8), pp.1035-1046.

[3] Gordis, L. and Gold, E.B., 1984. Epidemiology of pancreatic cancer. World journal of surgery, 8(6), pp.808-821.

[4] Smith, A., Poole, L., Dhanwada, K. and Goonesekere, N. C. W. (2016) “Identification of Candidate Biomarkers and Cancer Genes AHNAK2 and EPPK1 in Pancreatic Cancer”, Journal of Advances in Medicine and Medical Research, 18(8), pp. 1-8. doi: 10.9734/BJMMR/2016/28034.

[5] Ahmed El-Hadaad, H., Ahmed Wahba, H., Abozeed, W., Elnahas, W. and Roshdy, S. (2018) “Exocrine Pancreatic Cancer: A Clinico-epidemiologic Study”, Journal of Cancer and Tumor International, 7(3), pp. 1-7. doi: 10.9734/JCTI/2018/31933.

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