In order to avoid futile pancreatectomy or R2 pancreatic resections, preoperative evaluation of resectability by experienced surgeons and radiologists is important to distinguish between upfront resectable, BR-PC, and LA-PC in order to utilize the optimal therapeutic options. Not surprisingly, EOPC patients experience significantly fewer postoperative complications after surgical intervention than LOPC patients due to lower comorbidities of affected patients.
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As previously mentioned, there is no study to date that explicitly examines the behavior of EOPC in relation to neo adjuvant or palliative chemotherapy or radiotherapy. Nevertheless, a number of studies conducted in the general PC population — although not distinguishing between different patient age groups — show advantages of neoadjuvant chemotherapy over upfront surgery. Therefore, patients with these risk factors should be closely monitored. Since EOPC patients usually present with fewer comorbidities, they are more susceptible to a multi-modal therapy.
Concerning future treatment targets, comprehensive molecular investigations will particularly focus on cancer stem cells as well as tumor microenvironment including the stroma and immune system, for example, by analyzing tumor-infiltrating lymphocytes and cancer-associated fibroblast Figure 2. The evolution into personalized therapies in pancreatic ductal adenocarcinoma: challenges and opportunities.
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Whole genomes redefine the mutational landscape of pancreatic cancer. Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma. Nat Genet. Molecular subtyping of pancreatic cancer: translating genomics and transcriptomics into the clinic. J Cancer. Therapeutic implications of molecular subtyping for pancreatic cancer. Oncology Williston Park.
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However, most of these agents were ineffective, possibly because of the high molecular heterogeneity of the disease. An assessment of biomarkers is needed to identify the potential benefit from targeted therapy, and this may also provide important information to guide the use of precision medicine in clinical practice. The tumor microenvironment has attracted much research interest in the past decade. The pancreatic tumor microenvironment contains an abundant fibrotic stroma, which includes a variety of cell types and extracellular matrix ECM components, such as collagen, fibronectin, hyaluronic acid, and N-acetyl-glucosamine.
The stroma — not just a barrier for cancer cells — is critical in a variety of cellular processes, including tumor formation, invasion, metastasis, and drug resistance in PC. Recent studies have shown that PC stroma is associated with the modification of cancer cell metabolism, immune cell recruitment and the regulation of acinar-to-ductal metaplasia in the progression of PC. However, none of these genes are currently druggable.
Several new markers and therapeutic targets have been investigated, including mucins, mesothelin, and heavy metal transporters [ 17 , 18 , 19 ]. Recently, it has been shown that the zinc transporter ZIP4 is overexpressed in PC, and promotes tumor growth, metastasis, and cancer cachexia [ 20 , 21 ].
Targeting ZIP4 might be a novel treatment strategy for PC patients with dysregulated zinc homeostasis. PC remains a challenging disease to treat. Although survival statistics for PC patients are currently bleak, our understanding of the complicated etiology and molecular mechanisms of PC has improved tremendously in recent years.
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Early identification of PC is the most desirable objective. Efforts should be made to determine appropriate biomarkers for early tumor detection, and to open new perspectives on immunotherapy. Precision medicine and multidisciplinary team collaboration should become a trend in the treatment of PC, and will deliver the best therapeutic schedule for individual patients. Cancer statistics, CA Cancer J Clin. Challenges in diagnosis of pancreatic cancer. World J Gastroenterol. Improvement of surgical results for pancreatic cancer. Lancet Oncol. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head.
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Brief communication: a new combination in the treatment of advanced pancreatic cancer. Semin Oncol. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. Endoscopic ultrasonography-guided interstitial implantation of iodine seeds combined with chemotherapy in the treatment of unresectable pancreatic carcinoma: a prospective pilot study.
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Preoperative biliary drainage for cancer of the head of the pancreas. N Engl J Med. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Genomic analyses identify molecular subtypes of pancreatic cancer. Accessed 26 Oct Whole genomes redefine the mutational landscape of pancreatic cancer.
Phase III trial of bevacizumab in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer. Activity of mesothelin-specific chimeric antigen receptor T cells against pancreatic carcinoma metastases in a phase 1 trial. Clin Cancer Res. Aberrant expression of zinc transporter ZIP4 SLC39A4 significantly contributes to human pancreatic cancer pathogenesis and progression.
ZIP4 promotes muscle wasting and cachexia in mice with orthotopic pancreatic tumors by stimulating RAB27B-regulated release of extracellular vesicles from cancer cells. Download references. ML conceived and designed the study. All authors have read and approved the final version of the manuscript. Correspondence to Min Li. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions. Search all BMC articles Search. Abstract Pancreatic cancer is the fourth leading cause of cancer-related death in the United States, with increasing incidence.
Background Despite the continuous decline in overall cancer death rates, the mortality rate of pancreatic cancer PC remains high. Diagnosis: new biomarkers are still needed Patients with PC most commonly present with abdominal pain, weight loss, asthenia, and anorexia, with some patients also having jaundice. Surgery: the cure Surgery remains the only curative therapy for patients with PC.
Chemotherapy and radiotherapy: a tough choice For over a decade, gemcitabine was the standard first-line treatment for PC. Immunotherapy: role remains to be determined Immunotherapy is considered to be a promising treatment for many cancer types [ 12 ]. Precision medicine and target therapy: opportunities and obstacles Precision medicine is an emerging concept in oncology that offers improved outcomes by individualizing patient therapy.
Future novel perspectives The tumor microenvironment has attracted much research interest in the past decade.
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