scholarly journals Immune-Based Therapies and the Role of Microsatellite Instability in Pancreatic Cancer

Genes ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 33
Author(s):  
Michele Ghidini ◽  
Andrea Lampis ◽  
Milko B. Mirchev ◽  
Ali Fuat Okuducu ◽  
Margherita Ratti ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Current Knowledge ◽  
Treatment Options ◽  
Survival Rates ◽  
High Morbidity ◽  
Pancreatic Cancers ◽  
Repair Protein ◽  
Protein Functions

Pancreatic cancer is one of the most aggressive malignancies with limited treatment options thus resulting in high morbidity and mortality. Among all cancers, with a five-year survival rates of only 2–9%, pancreatic cancer holds the worst prognostic outcome for patients. To improve the overall survival, an earlier diagnosis and stratification of cancer patients for personalized treatment options are urgent needs. A minority of pancreatic cancers belong to the spectrum of Lynch syndrome-associated cancers and are characterized by microsatellite instability (MSI). MSI is a consequence of defective mismatch repair protein functions and it has been well characterized in other gastrointestinal tumors such as colorectal and gastric cancer. In the latter, high levels of MSI are linked to a better prognosis and to an increased benefit to immune-based therapies. Therefore, the same therapies could offer an opportunity of treatment for pancreatic cancer patients with MSI. In this review, we summarize the current knowledge about immune-based therapies and MSI in pancreatic cancer.

scholarly journals Establishment and Validation of a Genetic Label Associated With M2 Macrophage Infiltration to Predict Survival in Colon Cancer Patients and Assist Immunotherapy

2021 ◽  
Author(s):  
Boyang Xu ◽  
Ziqi Peng ◽  
Guanyu Yan ◽  
Ningning Wang ◽  
Moye Chen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Cancer Patients ◽  
Immune Cell ◽  
Checkpoint Inhibitors ◽  
Macrophage Infiltration ◽  
M2 Macrophage ◽  
High Morbidity ◽  
M2 Macrophages ◽  
Hub Genes

Abstract Background: Colon cancer is a kind of malignant tumor with high morbidity and mortality. Researchers have tried to interpret it from different perspectives and divide it into different subtypes in order to achieve individualized treatment. With the rise of immunotherapy, its value in the field of tumor has initially emerged. Based on the above background, from the perspective of immune infiltration, this study classified colon cancer according to the infiltration of M2 macrophages in patients with colon cancer and further explored it.Methods: Cibersort was used to analyze the level of immune cell infiltration in colon cancer patients in the TCGA database. WGCNA, Consensus Clustering analysis, Lasso analysis, and univariate KM analysis were used to screen and verify the hub genes associated with M2 macrophages. PCA was used to establish the M2 macrophage-related score—M2I Score. The correlation between M2I Score and somatic cell variation and microsatellite instability were analysed. Furthermore the correlation between M2 macrophage score and differences in immunotherapy sensitivity was also explored. Results: M2 macrophage infiltration was associated with poor prognosis. Four hub genes (ANKS4B, CTSD, TIMP1, and ZNF703) were selected as the progression-related genes associated with M2 macrophages. A stable and accurate M2I Score for M2 macrophages used in COAD was constructed based on four hub genes. M2I Score was positively correlated with tumor mutation load (TMB). The M2I Score of MSI-H group was higher than that of MSI-L group and MSS group. Combine with the TCIA database, we concluded that patients with a high M2I Score were more sensitive to PD-1 inhibitors and PD-1 inhibitors combined with CTLA-4 inhibitors. The low rating group may have better efficacy without immune checkpoint inhibitors or with CTLA4 inhibitors alone.Conclusion: Four prognostic hub genes associated with M2 macrophages were screened to establish the M2I Score and divided the patients into two subgroups: high M2I Score group and low M2I Score group. TMB, microsatellite instability and sensitivity to immunotherapy were higher in the high-rated group. PD-1 inhibitors or PD-1 combined with CTLA-4 inhibitors are preferred for patients in the high-rated group who are more sensitive to immunotherapy.

Effect of body mass index (BMI) on outcomes after surgical resection and adjuvant therapy for pancreatic cancer patients.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 185-185
Author(s):  
M. R. Khawaja ◽  
N. Zyromski ◽  
M. Yu ◽  
H. R. Cardenes ◽  
C. M. Schmidt ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Survival Rates ◽  
Disease Free Survival ◽  
University Hospital ◽  
Rank Test ◽  
Kaplan Meier ◽  
Significant Difference

185 Background: Obesity is one of the factors commonly associated with pancreatic cancer risk, but its prognostic role for survival is debatable. This study aimed to determine the role of BMI in treatment outcomes of pancreatic cancer patients (pts) undergoing surgical resection followed by adjuvant therapy. Methods: We retrospectively reviewed 165 consecutive pts with pancreatic cancer undergoing pancreaticoduodenectomy at Indiana University Hospital between 2004 and 2008. Fifty-three pts who received adjuvant treatment [gemcitabine alone (C-group): n=19; gemcitabine + radiotherapy (CRT-group): n=34] at our institution were included in the analysis. The Kaplan-Meier method was used to estimate the disease-free survival (DFS) and overall survival (OS); log-rank test was used to compare these outcomes between BMI groups (normal 18.5-24.99 kg/m2 vs. overweight/obese ≥ 25 kg/m2). Results: The sample comprised 53 pts (28 males; median age 62 yrs) with a median follow-up of 18.6 months (mos). Thirty pts (56.6%) had their BMIs recorded before the date of surgery, and 23 pts prior to starting adjuvant therapy. Two (3.8%) pts were underweight, 21 (39.6%) had a normal BMI and 30 (56.6%) were overweight/obese. There was no statistically significant difference in the median DFS of obese/overweight and normal BMI pts irrespective of adjuvant therapy (C or CRT) (14.47 vs. 11.80 mos; p= 0.111). Obese/overweight pts had a better median OS [25.2 vs. 14.6 mos; p=0.045 overall (25.7 vs. 16.9 mos; p= 0.143 for the CRT-group and 17.3 vs. 13.4 mos; p= 0.050 for the C-group)], 1-year survival [96.7% vs. 61.9%; p < 0.0001 overall (95% vs. 64.3%; p= 0.001 for the CRT-group, and 90% vs. 57.1%; p=0.016 with C)], and 2-year survival [52.6% vs. 25.4%; p < 0.0001 overall (60.0% vs. 30.0%; p=0.0001 for the CRT-group and 37.5% vs. 14.3%; p=0.0002 for the C-group)] than patients with normal BMI. Conclusions: In our experience, overweight/obese pts undergoing surgery followed by adjuvant therapy have better survival rates than patients with normal BMI. [Table: see text] No significant financial relationships to disclose.

scholarly journals Primary Thromboprophylaxis in Pancreatic Cancer Patients: Why Clinical Practice Guidelines Should Be Implemented

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 618 ◽  
Author(s):  
Dominique Farge ◽  
Barbara Bournet ◽  
Thierry Conroy ◽  
Eric Vicaut ◽  
Janusz Rak ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Practice ◽  
Cancer Patients ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Randomized Trials ◽  
Treatment Options ◽  
Locally Advanced ◽  
Ductal Adenocarcinoma ◽  
Recent Advances

Exocrine pancreatic ductal adenocarcinoma, simply referred to as pancreatic cancer (PC) has the worst prognosis of any malignancy. Despite recent advances in the use of adjuvant chemotherapy in PC, the prognosis remains poor, with fewer than 8% of patients being alive at 5 years after diagnosis. The prevalence of PC has steadily increased over the past decades, and it is projected to become the second-leading cause of cancer-related death by 2030. In this context, optimizing and integrating supportive care is important to improve quality of life and survival. Venous thromboembolism (VTE) is a common but preventable complication in PC patients. VTE occurs in one out of five PC patients and is associated with significantly reduced progression-free survival and overall survival. The appropriate use of primary thromboprophylaxis can drastically and safely reduce the rates of VTE in PC patients as shown from subgroup analysis of non-PC targeted placebo-controlled randomized trials of cancer patients and from two dedicated controlled randomized trials in locally advanced PC patients receiving chemotherapy. Therefore, primary thromboprophylaxis with a Grade 1B evidence level is recommended in locally advanced PC patients receiving chemotherapy by the International Initiative on Cancer and Thrombosis clinical practice guidelines since 2013. However, its use and potential significant clinical benefit continues to be underrecognized worldwide. This narrative review aims to summarize the main recent advances in the field including on the use of individualized risk assessment models to stratify the risk of VTE in each patient with individual available treatment options.

scholarly journals The Emerging Roles of ATP-Dependent Chromatin Remodeling Complexes in Pancreatic Cancer

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1859
Author(s):  
Nesrin Hasan ◽  
Nita Ahuja
Keyword(s):  
Pancreatic Cancer ◽  
Chromatin Remodeling ◽  
Treatment Options ◽  
Survival Rates ◽  
Pancreatic Tumors ◽  
Stem Cell Maintenance ◽  
Aggressive Cancer ◽  
Frequent Mutations ◽  
Chromatin Remodeling Complexes ◽  
Cancer Types

Pancreatic cancer is an aggressive cancer with low survival rates. Genetic and epigenetic dysregulation has been associated with the initiation and progression of pancreatic tumors. Multiple studies have pointed to the involvement of aberrant chromatin modifications in driving tumor behavior. ATP-dependent chromatin remodeling complexes regulate chromatin structure and have critical roles in stem cell maintenance, development, and cancer. Frequent mutations and chromosomal aberrations in the genes associated with subunits of the ATP-dependent chromatin remodeling complexes have been detected in different cancer types. In this review, we summarize the current literature on the genomic alterations and mechanistic studies of the ATP-dependent chromatin remodeling complexes in pancreatic cancer. Our review is focused on the four main subfamilies: SWItch/sucrose non-fermentable (SWI/SNF), imitation SWI (ISWI), chromodomain-helicase DNA-binding protein (CHD), and INOsitol-requiring mutant 80 (INO80). Finally, we discuss potential novel treatment options that use small molecules to target these complexes.

Effect of the addition of algenpantucel-L immunotherapy to standard adjuvant therapy on survival in patients with resected pancreas cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 236-236 ◽  
Author(s):  
J. M. Hardacre ◽  
M. F. Mulcahy ◽  
W. Small ◽  
M. Talamonti ◽  
J. C. Obel ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adjuvant Therapy ◽  
Treatment Options ◽  
Survival Rates ◽  
Phase Iii ◽  
Human Pancreatic Cancer ◽  
Open Label ◽  
Term Survival ◽  
Major Barrier ◽  
Pancreatic Cancer Cells

236 Background: Pancreatic cancer portends a poor prognosis with ∼4% long-term survival. Among the estimated 20% of patients who have resectable disease, the 1-/3-/5-year survival rates approximate only 70%/30%/18%, even with adjuvant therapy. Better treatment options are needed and addition of algenpantucel-L (HyperAcute-Pancreas) to standard adjuvant therapy is proposed to improve prospects for survival. Algenpantucel-L is composed of irradiated, live, allogeneic human pancreatic cancer cells expressing the enzyme α-1,3 galactosyl transferase (α-GT), which is the major barrier to xenotransplantation from lower mammals to humans (e.g., hyperacute rejection). Up to 2% of circulating human antibodies are directed against the α-GT epitope of algenpantucel-L and are the proposed mechanism of initiating the anti-tumor immune response. Methods: Open-label, single arm, multi-institutional phase II study (NLG0205) to evaluate algenpantucel-L + standard adjuvant therapy (RTOG-9704, JAMA, 2008: gemcitabine + 5-FU-XRT) for pancreatic cancer patients undergoing R0/R1 resection. Disease-free (DFS) and overall survival (OS) are the primary and secondary endpoints, respectively. Results: 73 patients (70 evaluable, 15 month median follow up) received gemcitabine + 5-FU-XRT + algenpantucel-L (mean 12 doses, range 1-14). Demographics and prognostic factors: median age 62 years, 47% female, 81.4% lymph node positive, median tumor size 3.2 cm (range 2-15 cm; 26% > 4cm) and 24% post-operative CA 19-9 > 90. Kaplan-Meier estimated survival rates at 12 and 24 months are 91% and 54%, respectively, comparing favorably to 63% and 32% expected based on the nomogram described by Brennan et al (Ann Surg, 2004). Likewise, the current median DFS of 16 months compares favorably to the 11 months observed in RTOG 9704. OS data continues to mature, with 74% still censored. Algenpantucel-L was well tolerated with no likely/directly attributable grade 3 SAEs. The most common adverse events were injection site pain and induration. Conclusions: Addition of algenpantucel-L to standard adjuvant therapy for resected pancreatic cancer may improve survival. A phase III study began patient enrollment in May 2010. [Table: see text]

scholarly journals Detection of Pancreatic Cancer Biomarkers Using Mass Spectrometry

2014 ◽  
Vol 13s7 ◽  
pp. CIN.S16341
Author(s):  
Kiyoun Kim ◽  
Soohyun Ahn ◽  
Johan Lim ◽  
Byong Chul Yoo ◽  
Jin-Hyeok Hwang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Cancer Patients ◽  
Surgical Resection ◽  
Missing Values ◽  
Survival Rates ◽  
Classification Methods ◽  
Increased Risk ◽  
Patients With Diabetes

Background Pancreatic cancer is the fourth leading cause of cancer-related deaths. Therefore, in order to improve survival rates, the development of biomarkers for early diagnosis is crucial. Recently, diabetes has been associated with an increased risk of pancreatic cancer. The aims of this study were to search for novel serum biomarkers that could be used for early diagnosis of pancreatic cancer and to identify whether diabetes was a risk factor for this disease. Methods Blood samples were collected from 25 patients with diabetes (control) and 93 patients with pancreatic cancer (including 53 patients with diabetes), and analyzed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF/MS). We performed preprocessing, and various classification methods with imputation were used to replace the missing values. To validate the selection of biomarkers identified in pancreatic cancer patients, we measured biomarker intensity in pancreatic cancer patients with diabetes following surgical resection and compared our results with those from control (diabetes-only) patients. Results By using various classification methods, we identified the commonly splitting protein peaks as m/z 1,465, 1,206, and 1,020. In the follow-up study, in which we assessed biomarkers in pancreatic cancer patients with diabetes after surgical resection, we found that the intensities of m/z at 1,465, 1,206, and 1,020 became comparable with those of diabetes-only patients.

Postoperative complications and survival rates for pancreatic cancer patients

2011 ◽  
Vol 123 (3-4) ◽  
pp. 94-99 ◽  
Author(s):  
Jana Kaťuchová ◽  
Juray Bober ◽  
Jozef Radoňak
Keyword(s):  
Pancreatic Cancer ◽  
Postoperative Complications ◽  
Cancer Patients ◽  
Survival Rates

scholarly journals Elucidating the Role of Extracellular Vesicles in Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5669
Author(s):  
Akbar Lulu Marzan ◽  
Sarah Elizabeth Stewart
Keyword(s):  
Drug Delivery ◽  
Pancreatic Cancer ◽  
Survival Rate ◽  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Current Knowledge ◽  
Treatment Options ◽  
Metabolic Dysfunction ◽  
Underlying Mechanisms

Pancreatic cancer is one of the deadliest cancers worldwide, with a 5-year survival rate of less than 10%. This dismal survival rate can be attributed to several factors including insufficient diagnostics, rapid metastasis and chemoresistance. To identify new treatment options for improved patient outcomes, it is crucial to investigate the underlying mechanisms that contribute to pancreatic cancer progression. Accumulating evidence suggests that extracellular vesicles, including exosomes and microvesicles, are critical players in pancreatic cancer progression and chemoresistance. In addition, extracellular vesicles also have the potential to serve as promising biomarkers, therapeutic targets and drug delivery tools for the treatment of pancreatic cancer. In this review, we aim to summarise the current knowledge on the role of extracellular vesicles in pancreatic cancer progression, metastasis, immunity, metabolic dysfunction and chemoresistance, and discuss their potential roles as biomarkers for early diagnosis and drug delivery vehicles for treatment of pancreatic cancer.

scholarly journals P2RY12-Inhibitors Reduce Cancer-Associated Thrombosis and Tumor Growth in Pancreatic Cancers

2021 ◽  
Vol 11 ◽  
Author(s):  
Ana Luisa Palacios-Acedo ◽  
Soraya Mezouar ◽  
Diane Mège ◽  
Lydie Crescence ◽  
Christophe Dubois ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Tumor Growth ◽  
Survival Rates ◽  
Cancer Growth ◽  
Primary Tumors ◽  
Trousseau’S Syndrome ◽  
Pancreatic Cancers ◽  
Cancer Associated Thrombosis

Platelet function can be modified by cancer cells to support tumor growth, causing alterations in the delicate hemostatic equilibrium. Cancer-cell and platelet interactions are one of the main pillars of Trousseau’s syndrome: a paraneoplastic syndrome with recurring and migrating episodes of thrombophlebitis. Altogether, this leads to a four-fold risk of thrombotic events in cancer patients, which in turn, portend a poor prognosis. We previously demonstrated that anti-P2RY12 drugs inhibit cancer-associated-thrombosis and formation of tumor metastasis in pancreatic cancer models. Here, we aimed to (1) compare the effects of aspirin and clopidogrel on pancreatic cancer prevention, (2) characterize the effects of clopidogrel (platelet P2RY12 inhibitor) on cancer-associated thrombosis and cancer growth in vivo, (3) determine the effect of P2RY12 across different digestive-tract cancers in vitro, and (4) analyze the expression pattern of P2RY12 in two different cancer types affecting the digestive system. Clopidogrel treatment resulted in better survival rates with smaller primary tumors and less metastasis than aspirin treatment. Clopidogrel was also more effective than aspirin at dissolving spontaneous endogenous thrombi in our orthotopic advanced cancer mouse model. P2RY12 expression gives pancreatic adenocarcinomas proliferative advantages. In conclusion, we propose the hypothesis that clopidogrel should be further studied to target and prevent Trousseau’s syndrome; as well as diminish cancer growth and spread. However, more studies are required to determine the implicated pathways and effects of these drugs on cancer development.

Emerging Insights into Wnt/β-catenin Signaling in Head and Neck Cancer

2018 ◽  
Vol 97 (6) ◽  
pp. 665-673 ◽  
Author(s):  
K.A. Alamoud ◽  
M.A. Kukuruzinska
Keyword(s):  
Head And Neck Cancer ◽  
Head And Neck ◽  
Neck Cancer ◽  
Target Genes ◽  
Treatment Options ◽  
Survival Rates ◽  
Central Component ◽  
High Morbidity ◽  
Matrix Remodeling ◽  
Wide Range

Head and neck cancer presents primarily as head and neck squamous cell carcinoma (HNSCC), a debilitating malignancy fraught with high morbidity, poor survival rates, and limited treatment options. Mounting evidence indicates that the Wnt/β-catenin signaling pathway plays important roles in the pathobiology of HNSCC. Wnt/β-catenin signaling affects multiple cellular processes that endow cancer cells with the ability to maintain and expand immature stem-like phenotypes, proliferate, extend survival, and acquire aggressive characteristics by adopting mesenchymal traits. A central component of canonical Wnt signaling is β-catenin, which balances its role as a structural component of E-cadherin junctions with its function as a transcriptional coactivator of numerous target genes. Recent genomic characterization of head and neck cancer revealed that while β-catenin is not frequently mutated in HNSCC, its activity is unchecked by more common mutations in genes encoding upstream regulators of β-catenin, NOTCH1, FAT1, and AJUBA. Wnt/β-catenin signaling affects a wide range epigenetic and transcriptional activities, mediated by the interaction of β-catenin with different transcription factors and transcriptional coactivators and corepressors. Furthermore, Wnt/β-catenin functions in a network with many signaling and metabolic pathways that modulate its activity. In addition to its effects on tumor epithelia, β-catenin activity regulates the tumor microenvironment by regulating extracellular matrix remodeling, fibrotic processes, and immune response. These multifunctional oncogenic effects of β-catenin make it an attractive bona fide target for HNSCC therapy.

Sign in / Sign up

Export Citation Format

Share Document