Plasma KRAS mutations predict the early recurrence after surgical resection of pancreatic cancer

Cancer Biol Ther. 2021 Oct 10:1-7. doi: 10.1080/15384047.2021.1980312. Online ahead of print.ABSTRACTBACKGROUND: The technique to analyze circulating tumor DNA (ctDNA) in body fluid (so-called "liquid biopsy") is recently developed.AIMS: Our aim was to assess the utility of liquid biopsy for predicting progression of pancreatic ductal adenocarcinoma (PDAC) after surgical resection or chemotherapy.METHODS: A total of 72 patients with PDAC were retrospectively enrolled for this study, 33 treated surgically and 39 given chemotherapy, either FOLFIRINOX (oxaliplatin/irinotecan/fluorouracil/leucovorin) or gemcitabine plus nab-paclitaxel. Prior to treatment, patients were screened for the presence of KRAS mutations (G12D and G12V) in plasma using droplet digital polymerase chain reaction, and outcomes were compared.RESULTS: KRAS mutations were identified in plasma samples of 12 patients (36%) underwent surgical resection. Patients with plasma KRAS mutations had significantly shorter disease-free survival (DFS) and overall survival (p
Source: Cancer Biology and Therapy - Category: Cancer & Oncology Authors: Source Type: research

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sa A. Cardone Currently, the median overall survival of PDAC patients rarely exceeds 1 year and has an overall 5-year survival rate of about 9%. These numbers are anticipated to worsen in the future due to the lack of understanding of the factors involved in its strong chemoresistance. Chemotherapy remains the only treatment option for most PDAC patients; however, the available therapeutic strategies are insufficient. The factors involved in chemoresistance include the development of a desmoplastic stroma which reprograms cellular metabolism, and both contribute to an impaired response to therapy. PDAC stroma is compos...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
CONCLUSION: SF3B1 overexpression represents a therapeutic vulnerability in PDAC, as altered splicing can be targeted with Pladienolide-B both in cancer cells and CSCs, paving the way for novel therapies for this lethal cancer.PMID:34857016 | DOI:10.1186/s13046-021-02153-9
Source: Cell Research - Category: Cytology Authors: Source Type: research
Condition:   Pancreatic Cancer Intervention:   Radiation: High Dose Rate Brachytherapy (HDR) Intraoperative Radiation Therapy (IORT) Sponsor:   Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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 ...
Source: Cancer and Metastasis Reviews - Category: Cancer & Oncology Source Type: research
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 in...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Neoplasma. 2021 Nov 25:210924N1360. doi: 10.4149/neo_2021_210924N1360. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive type of malignancy with one of the worst prognoses amongst any type of cancer. Surgery is applicable only to the limited number of patients with locally resectable tumors and currently represents the only curative treatment option. Treatment with chemotherapy and radiotherapy can only extend patient survival. Despite advances in conventional therapies, the five-year survival of PDAC remained largely unchanged. New in vitro and in vivo models are therefore urgent...
Source: Neoplasma - Category: Cancer & Oncology Authors: Source Type: research
Objective: To identify the survival benefit of different adjuvant approaches and factors influencing their efficacy after upfront resection of pancreatic ductal adenocarcinoma (PDAC). Summary Background Data: The optimal adjuvant approach for PDAC remains controversial. Methods: Patients from the National Cancer Database who underwent upfront PDAC resection from 2010 to 2014 were analyzed to determine clinical outcomes of different adjuvant treatment approaches, stratified according to pathologic characteristics. Factors associated with overall survival were identified with multivariable logistic regressi...
Source: Annals of Surgery - Category: Surgery Tags: ORIGINAL ARTICLES Source Type: research
Eur J Pharm Biopharm. 2021 Nov 18:S0939-6411(21)00278-2. doi: 10.1016/j.ejpb.2021.11.005. Online ahead of print.ABSTRACTChemotherapy is the recommended treatment for patients with advanced pancreatic ductal adenocarcinoma (PDAC). However, efficacy of traditional chemotherapy is not satisfactory due to the presence of a dense dysplastic tumor stroma which prevents drug accumulation in and deep penetration into tumors. To overcome these obstacles, we designed and synthesized peptide dendrimers as potentiators of conventional chemotherapy. The dendrimers markedly promoted free doxorubicin accumulation and penetration deeply i...
Source: European Journal of Pharmaceutics and Biopharmaceutics - Category: Drugs & Pharmacology Authors: Source Type: research
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