Metabolic reprogramming by driver mutation-tumor microenvironment interplay in pancreatic cancer: new therapeutic targets

AbstractPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers globally with a mortality rate exceeding 95% and very limited therapeutic options. A hallmark of PDAC is its acidic tumor microenvironment, further characterized by excessive fibrosis and depletion of oxygen and nutrients due to poor vascularity. The combination of PDAC driver mutations and adaptation to this hostile environment drives extensive metabolic reprogramming of the cancer cells toward non-canonical metabolic pathways and increases reliance on scavenging mechanisms such as autophagy and macropinocytosis. In addition, the cancer cells benefit from metabolic crosstalk with nonmalignant cells within the tumor microenvironment, including pancreatic  stellate cells, fibroblasts, and endothelial and immune cells. Increasing evidence shows that this metabolic rewiring is closely related to chemo- and radioresistance and immunosuppression, causing extensive treatment failure. Indeed, stratification of human PDAC tumors into subtypes based on thei r metabolic profiles was shown to predict disease outcome. Accordingly, an increasing number of clinical trials target pro-tumorigenic metabolic pathways, either as stand-alone treatment or in conjunction with chemotherapy. In this review, we highlight key findings and potential future directions of pancreatic cancer metabolism research, specifically focusing on novel therapeutic opportunities.
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research

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DISCUSSION: An adequate long-term control of pain symptoms in patients with mPDAC is an unmet clinical need. Despite improvements in systemic treatment, local complications due to pPCa remain a clinical challenge. We hypothesize that patients with mPDAC will benefit from a local treatment of the pPCa by MR-guided SBRT in terms of a durable pain control with a simultaneously favorable safe toxicity profile translating into an improvement of quality-of-life.TRIAL REGISTRATION: German Registry for Clinical Trials (DRKS): DRKS00025801. Meanwhile the study is also registered at ClinicalTrials.gov with the Identifier: NCT0511421...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research
rt Charles D. Lopez Adel Kardosh Emerson Y. Chen Kenneth G. Bensch Nima Nabavizadeh Charles R. Thomas Skye C. Mayo Brett C. Sheppard Aaron Grossberg The role of neoadjuvant chemoradiotherapy and/or chemotherapy (neoCHT) in patients with pancreatic ductal adenocarcinoma (PDAC) is poorly defined. We hypothesized that patients who underwent neoadjuvant therapy (NAT) would have improved systemic therapy delivery, as well as comparable perioperative complications, compared to patients undergoing upfront resection. This is an IRB-approved retrospective study of potentially resectable PDAC patients treated w...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Front Oncol. 2022 Jan 6;11:730646. doi: 10.3389/fonc.2021.730646. eCollection 2021.ABSTRACTPURPOSE: We investigated potential factors, including clinicopathological features, treatment modalities, neutrophil-to-lymphocyte ratio (NLR), carbohydrate antigen (CA) 19-9 level, tumor responses correlating with overall survival (OS), local progression (LP), and distant metastases (DMs), in patients with locally advanced pancreatic cancer (LAPC) who received definitive radiotherapy (RT).METHODS: We retrospectively analyzed demographic characteristics; biologically effective doses (BED10, calculated with an α/β of 10) of...
Source: Cancer Control - Category: Cancer & Oncology Authors: Source Type: research
Conclusions: The analysis of the Kras gene status could be used to predict therapeutic responses to GA and prognosis in unresectable PDAC patients.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
AbstractBackgroundAdjuvant chemotherapy (ACT) is widely accepted in patients with pancreatic ductal adenocarcinoma (PDAC) after surgery; however, effective models for predicting ACT response are scarce. Thus, the objective of this study was to develop a novel signature for predicting its response and overall survival (OS) in resected PDAC patients.MethodsA total of 50 PDAC patients with the transcriptome expression profiles, information about chemotherapy, and relevant clinical data were retrieved from the Cancer Genome Atlas (TCGA), and twenty-nine patients with tissue specimens and clinical data from our hospital were in...
Source: Journal of Gastrointestinal Surgery - Category: Surgery Source Type: research
According to GLOBOCAN 2020, pancreatic cancer is currently the 7th most common fatal cancer worldwide [1]. However, in some regions as Europe and North America, it represents the 4th most common cause of cancer death [2,3]. Pancreatic adenocarcinoma (PDAC) accounts for 80% of all pancreatic cancers. [4] It is a neoplasm with poor prognosis, even for early stages. The 5-year relative survival is 41.5% for patients with localized disease, 14.4% for regional disease and 3% for those with metastatic disease [5 –7].
Source: Cancer Treatment Reviews - Category: Cancer & Oncology Authors: Source Type: research
AbstractBackgroundAdjuvant chemotherapy (ACT) is widely accepted in patients with pancreatic ductal adenocarcinoma (PDAC) after surgery; however, effective models for predicting ACT response are scarce. Thus, the objective of this study was to develop a novel signature for predicting its response and overall survival (OS) in resected PDAC patients.MethodsA total of 50 PDAC patients with the transcriptome expression profiles, information about chemotherapy, and relevant clinical data were retrieved from the Cancer Genome Atlas (TCGA), and twenty-nine patients with tissue specimens and clinical data from our hospital were in...
Source: Journal of Gastrointestinal Surgery - Category: Surgery Source Type: research
OverviewThis manuscript summarizes an excellent debate from the 2021 SSAT/Pancreas Club symposium on arterial resection in pancreas cancer. Two world-recognized experts, Professor Ugo Boggi from Pisa, IT, and Dr. Mark Truty from the Mayo Clinic in Rochester, MN, offered their views on the role of arterial resection in locally advanced pancreas ductal adenocarcinoma. Both speakers have extensive experience pushing the technical envelope with extended vascular resection in pancreatectomy. However, both highlight important concepts of resectability extending well beyond technique: namely, patient global physiology, tumor biol...
Source: Journal of Gastrointestinal Surgery - Category: Surgery Source Type: research
Oxysterol-binding protein 2 (OSBP2) is crucial for promoting the growth and development of cancers; however, its effects on pancreatic ductal adenocarcinoma (PDAC) are still unclear. Here, we report that OSBP2 is an efficient tumor-associated protein to lead to extremely malignant characteristics in PDAC. We discovered that increased OSBP2 expression in primary tumors was associated with shorter survival in PDAC patients. Therefore, we used immunohistochemistry (IHC) to analyze the levels of OSBP2 expression in PDAC tissues and adjacent paracancerous tissues. We used wound healing and Transwell assays to evaluate the effec...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
OverviewThis manuscript summarizes an excellent debate from the 2021 SSAT/Pancreas Club symposium on arterial resection in pancreas cancer. Two world-recognized experts, Professor Ugo Boggi from Pisa, IT, and Dr. Mark Truty from the Mayo Clinic in Rochester, MN, offered their views on the role of arterial resection in locally advanced pancreas ductal adenocarcinoma. Both speakers have extensive experience pushing the technical envelope with extended vascular resection in pancreatectomy. However, both highlight important concepts of resectability extending well beyond technique: namely, patient global physiology, tumor biol...
Source: Journal of Gastrointestinal Surgery - Category: Surgery Source Type: research
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