Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by early metastasis, late detection, and poor prognosis. Progress towards effective therapy has been slow despite significant efforts. Novel treatment approaches are desperately needed and autophagy, an evolutionary conserved process through which proteins and organelles are recycled for use as alternative energy sources, may represent one such target. Although incompletely understood, there is growing evidence suggesting that autophagy may play a role in PDAC carcinogenesis, metastasis, and survival. Early clinical trials involving autophagy inhibiting agents, either alone or in combination with chemotherapy, have been disappointing. Recently, evidence has demonstrated synergy between the MAPK pathway and autophagy inhibitors in PDAC, suggesting a promising therapeutic intervention. In addition, novel agents, such as ONC212, have preclinical activity in pancreatic cancer, in part through autophagy inhibition. We discuss autophagy in PDAC tumorigenesis, metabolism, modulation of the immune response, and preclinical and clinical data with selected autophagy modulators as therapeutics.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research

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J Pathol Clin Res. 2022 Jan 17. doi: 10.1002/cjp2.259. Online ahead of print.ABSTRACTImmunotherapy targeting programmed cell death-1 (PD-1) has considerably improved the prognosis of patients with advanced cancers; however, its efficacy in the treatment of pancreatic ductal adenocarcinoma (PDAC) is unfavourable. To address the issue of PDAC immunotherapy, we investigated the expression of two PD-1 ligands, PD-L1 and PD-L2, in PDAC, analysed their role in survival, and explored their correlation with clinicopathological features, immune infiltration, and DNA damage response molecules. Immunohistochemistry was performed on 2...
Source: Cell Research - Category: Cytology Authors: Source Type: research
Breast Dis. 2022;41(1):187-189. doi: 10.3233/BD-210042.ABSTRACTThe 42-year-old patient, diagnosed with Stage IIA breast cancer, completed the postoperative adjuvant chemotherapy and radiotherapy. At the 11th year of diagnosis, a 3 cm tumor was detected in the pancreas and pancreatectomy was performed. Although the diagnosis of primary pancreatic adenocarcinoma was made at first, then the pancreatic metastasis of breast cancer was discovered. Pancreatic metastasis of breast cancer is extremely rare, and a limited number of patients have been reported in the literature. Here, we report an additional case of this rare tumor a...
Source: Breast Disease - Category: Cancer & Oncology Authors: Source Type: research
AbstractBackgroundFor prognostic evaluation of pancreatic ductal adenocarcinoma (PDAC), the only well-established serum marker is carbohydrate antigen CA19-9. To improve the accuracy of survival prediction, we tested the efficacy of inflammatory serum markers.MethodsA preoperative serum panel comprising 48 cytokines plus high-sensitivity CRP (hs-CRP) was analyzed in 173 stage I –III PDAC patients. Analysis of the effect of serum markers on survival utilized the Cox regression model, with the most promising cytokines chosen with the aid of the lasso method. We formed a reference model comprising age, gender, tumor sta...
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research
AbstractIn this short report we present a series of thirteen patients with locally advanced, unresectable, pancreatic cancer treated with a COMBO-Therapy consisting of: STEP-1: induction chemotherapy; STEP-2: concomitant chemoradiotherapy; STEP-3: stereotactic body radiotherapy boost. After four weeks from the end of each step all patients had a re-staging and a surgical re-evaluation. All patients completed STEP-1 and STEP-2. STEP-3 has been successfully delivered to 8/13 patients with a median dose of 12  Gy (range 10–21 Gy) in 1–3 fractions. The median LC was 20 months (range 10–32) with...
Source: La Radiologia Medica - Category: Radiology Source Type: research
Conclusion: We propose an efficient screening system for PDAC with high accuracy by liquid biopsy and potential biomarkers useful for assessing NAC performance.PMID:35003367 | PMC:PMC8734412 | DOI:10.7150/jca.63244
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research
ConclusionsHigh-quality data for PDAC patients undergoing upfront surgery is scarce. Meta-analysis from the included studies showed a significantly shorter OS and DFS compared to recently published studies focusing on adjuvant combination chemotherapy, suggesting that the latter may overestimate survival due to the exclusion of most patients scheduled for upfront surgery.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSIONS: Endoscopic duodenal stent placement showed similar or better clinical outcomes than gastrojejunostomy. Thus, it might be a promising option in patients with good performance status.PMID:34969090 | DOI:10.1093/jjco/hyab194
Source: Clinical Genitourinary Cancer - Category: Cancer & Oncology Authors: Source Type: research
Transl Oncol. 2021 Dec 23;16:101321. doi: 10.1016/j.tranon.2021.101321. Online ahead of print.ABSTRACTCirculating tumor cells (CTCs) have emerged as liquid biopsy biomarker providing non-invasive assessment of cancer progression and biology. We investigated whether longitudinal analysis of CTCs could monitor disease progression, response to chemotherapy, and survival in patients with unresectable pancreatic ductal adenocarcinoma (PDAC). A total of 52 patients with PDAC were prospectively enrolled in this study. Peripheral blood samples were serially collected at the time of diagnosis and after chemotherapy with clinical as...
Source: Translational Oncology - Category: Cancer & Oncology Authors: Source Type: research
CONCLUSIONS: Endoscopic ultrasound-guided 32P microparticle implantation has an acceptable safety profile. This study also suggests clinically relevant benefits of combining 32P microparticles with standard-of-care systemic chemotherapy for patients with unresectable LAPC.PMID:34953400 | DOI:10.1016/j.esmoop.2021.100356
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research
Condition:   Pancreatic Ductal Adenocarcinoma, PDAC Intervention:   Sponsor:   Ruijin Hospital Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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