Precision Therapy of Pancreatic Cancer: From Bench to Bedside.
Ontology highlight
ABSTRACT: Background
Pancreatic ductal adenocarcinoma (PDAC), with a mortality rate of 94% and a 5-year-survival rate of only 8%, is one of the deadliest cancer entities worldwide, and early diagnostic methods as well as effective therapies are urgently needed.Summary
This review summarizes current clinical procedure and recent developments of oncological therapy in the palliative setting of metastatic PDAC. It further gives examples of successful, as well as failed, targeted therapy approaches and finally discusses promising ongoing research into the decade-old question of the "undruggability" of KRAS.Key messages
Bench-driven concepts change the clinical landscape from "one size fits all" towards precision medicine. With growing insight into the molecular mechanisms of pancreatic cancer the era of targeted therapy in PDAC is gaining a new momentum.
SUBMITTER: Ciecielski KJ
PROVIDER: S-EPMC7590788 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Pancreatic ductal adenocarcinoma (referred here as pancreatic cancer) is a lethal disease with the worst prognosis among all solid tumors. Surgical resection represents the only hope for cure but it is possible only in patients that present with local disease (about 20% of cases). Whether dismal prognosis of pancreatic cancer is a result of late diagnosis or early dissemination to distant organ is still a debate. Moreover, this disease shows an intrinsic chemotherapeutic resistance that has been mainly ascribed to the presence of a dense stromal reaction that significantly impairs drugs delivery. Clinical management of pancreatic cancer patients relies on few molecular markers (e.g., the diagnostic marker CA19-9) that, however, present several limitations to their use. The clinical usefulness of somatic alterations in well-characterized genes (such as KRAS and TP53), whose detection is technically feasible in different biological samples, has been extensively investigated leading to inconsistent results. Furthermore, none of the candidate molecular markers identified in recent years has shown an appropriate clinical performance and therefore none is routinely used. This depicts a scenario where the identification of novel and effective clinical biomarkers is mandatory. Very recent genome-wide comprehensive studies have shed light on the high degree of genetic complexity and heterogeneity of the pancreatic cancers. Although far from being introduced into the clinical settings, results from those studies are expected to change definitively the perspective through which we look at the clinical management of pancreatic cancer patients towards a personalized cancer medicine.
| S-EPMC3419918 | biostudies-literature
Project description: Not available
| S-EPMC3806061 | biostudies-literature
Project description:The incidence of pancreatic cancer has been increasing while its 5-year survival rate has not changed in decades. In the era of personalized medicine, immunotherapy has emerged as a promising treatment modality in a variety of malignancies, including pancreatic cancer. This review will discuss the unique pancreatic tumor microenvironment, including the cells and receptors that transform the pancreas from its normal architecture into a complex mix of suppressor immune cells and dense extracellular matrix that allows for the unrestricted growth of cancer cells. Next, we will highlight the recently completed immunotherapy clinical trials in pancreatic cancer. Finally, we will explore the on-going immunotherapy clinical trials and future directions of this engaging and changing field.
| S-EPMC4791889 | biostudies-literature
Project description:In the last forty years the pancreatic cancer treatment has made advances, however; still novel drugs are needed. It is known that the five year survival rate remains around 5%. The best treatment option still remains surgery, if patients are diagnosed early. In the last decade the biology of pancreatic cancer has been vastly explored and novel agents such as; tyrosine kinase agents, or vaccines have been added as a treatment perspective. The big challenge is now to translate this knowledge in better outcomes for patients. In this current review we will present information from pancreatic cancer diagnosis to molecular pathways and treatment options; current and future.
| S-EPMC4876273 | biostudies-other
Project description:Spherical Nucleic Acids (SNAs) emerged as a new class of nanotherapeutics consisting of a nanoparticle core densely functionalized with a shell of radially oriented synthetic oligonucleotides. The unique three-dimensional architecture of SNAs protects the oligonucleotides from nuclease-mediated degradation, increases oligonucleotide bioavailability, and in the absence of auxiliary transfection agents, enables robust uptake into tumor and immune cells through polyvalent association with cell surface pattern recognition receptors. When composed of gene-regulatory small interfering (si)RNA or immunostimulatory DNA or RNA oligonucleotides, SNAs silence gene expression and induce immune responses superior to those raised by the oligonucleotides in their "free" form. Early phase clinical trials of gene-regulatory siRNA-based SNAs in glioblastoma (NCT03020017) and immunostimulatory Toll-like receptor 9 (TLR9)-agonistic SNAs carrying unmethylated CpG-rich oligonucleotides in solid tumors (NCT03086278) have shown that SNAs represent a safe, brain-penetrant therapy for inhibiting oncogene expression and stimulating immune responses against tumors. This review focuses on the application of SNAs as precision cancer therapeutics, summarizes the findings from first-in-human clinical trials of SNAs in solid tumors, describes the most recent preclinical efforts to rationally design next-generation multimodal SNA architectures, and provides an outlook on future efforts to maximize the anti-neoplastic activity of the SNA platform.
| S-EPMC8996871 | biostudies-literature
Project description:Pancreatic cancer is the fourth leading cause of cancer death among men and women in the United States, and pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of pancreatic cancer cases. PDAC is one of the most lethal gastrointestinal malignancies with an overall five-year survival rate of ~10%. Developing effective therapeutic strategies against pancreatic cancer is a great challenge. Novel diagnostic, prognostic, and therapeutic strategies are an immediate necessity to increase the survival of pancreatic cancer patients. So far, studies have demonstrated microRNAs (miRNAs) as sensitive biomarkers because of their significant correlation with disease development and metastasis. The miRNAs have been shown to be more stable inside membrane-bound vesicles in the extracellular environment called exosomes. Varieties of miRNAs are released into the body fluids via exosomes depending on the normal physiological or pathological conditions of the body. In this review, we discuss the recent findings on the diagnostic, prognostic, and therapeutic roles of exosomal miRNAs in pancreatic cancer.
| S-EPMC8199777 | biostudies-literature
Project description:Pancreatic cancer is one of the deadliest cancer types urgently requiring effective therapeutic strategies. Autophagy occurs in several compartments of pancreatic cancer tissue including cancer cells, cancer associated fibroblasts, and immune cells where it can be subjected to a multitude of stimulatory and inhibitory signals fine-tuning its activity. Therefore, the effects of autophagy on pancreatic carcinogenesis and progression differ in a stage and context dependent manner. In the initiation stage autophagy hinders development of preneoplastic lesions; in the progression stage however, autophagy promotes tumor growth. This double-edged action of autophagy makes it a hard therapeutic target. Indeed, autophagy inhibitors have not yet shown survival improvements in clinical trials, indicating a need for better evaluation of existing results and smarter targeting techniques. Clearly, the role of autophagy in pancreatic cancer is complex and many aspects have to be considered when moving from the bench to the bedside.
| S-EPMC7226443 | biostudies-literature
Project description:Diabetes mellitus (DM) is a metabolic disorder associated with accelerated atherogenesis and an increased risk of atherothrombotic complications. Multiple mechanisms contribute to the pro-thrombotic status which characterizes DM patients underscoring the importance of antiplatelet therapies used for secondary prevention in these patients. For many years, dual antiplatelet therapy (DAPT) with aspirin and the P2Y12 inhibitor clopidogrel has represented the mainstay of treatment following an acute coronary syndrome (ACS) or in patients undergoing percutaneous coronary interventions (PCI). Although DAPT reduces the incidence of atherothrombotic recurrences, these rates remain high in DM patients underscoring the need for more efficacious therapies. Oral platelet P2Y12 receptor inhibitors with enhanced potency, such as prasugrel and ticagrelor, as well as antiplatelet therapies such as vorapaxar inhibiting the thrombin-mediated platelet signaling pathway, constitute treatment opportunities for patients with DM and have shown to be associated with a greater reduction in ischemic recurrences, albeit at the cost of more bleeding. This article reviews currently available antiplatelet agents and delivers an update on the advances and drawbacks of these agents used for secondary prevention in DM patients experiencing an ACS or undergoing PCI.
| S-EPMC6232350 | biostudies-literature
Project description:Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. Keywords: genomics, diagnosis, microarray, calprotectin
2006-08-29 | GSE5663 | GEO
Project description:MicroRNAs (miRNAs) are small, single-stranded, noncoding RNAs that can post-transcriptionally regulate the expression of various oncogenes and tumor suppressor genes. Dysregulated expression of many miRNAs have been shown to mediate the signaling pathways critical in the multistep carcinogenesis of colorectal cancer (CRC). MiRNAs are stable and protected from RNase-mediated degradation, thereby enabling its detection in biological fluids and archival tissues for biomarker studies. This review focuses on the role and application of miRNAs in the prognosis and therapy of CRC. While stage II CRC is potentially curable by surgical resection, a significant percentage of stage II CRC patients do develop recurrence. MiRNA biomarkers may be used to stratify such high-risk population for adjuvant chemotherapy to provide better prognoses. Growing evidence also suggests that miRNAs are involved in the metastatic process of CRC. Certain of these miRNAs may thus be used as prognostic biomarkers to identify patients more likely to have micro-metastasis, who could be monitored more closely after surgery and/or given more aggressive adjuvant chemotherapy. Intrinsic and acquired resistance to chemotherapy severely hinders successful chemotherapy in CRC treatment. Predictive miRNA biomarkers for response to chemotherapy may identify patients who will benefit the most from a particular regimen and also spare the patients from unnecessary side effects. Selection of patients to receive the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Lastly, forced expression of tumor suppressor miRNA or silencing of oncogenic miRNA in tumors by gene therapy can also be adopted to treat CRC alone or in combination with other chemotherapeutic drugs.
| S-EPMC6054943 | biostudies-literature