scholarly journals What is the role of PARP inhibitors in pancreatic cancer?

2020 ◽  
Vol 20 (11) ◽  
pp. 913-918
Author(s):  
Ritika Halder ◽  
Rachna T. Shroff
Keyword(s):  
Pancreatic Cancer ◽  
Parp Inhibitors

Frequency of BRCA1 5382insC mutations in Russian non-selected pancreatic cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15165-e15165
Author(s):  
Alexey Kashintsev
Keyword(s):  
Pancreatic Cancer ◽  
Family History ◽  
Founder Mutation ◽  
Brca1 Mutation ◽  
Parp Inhibitors ◽  
Mutation Carriers ◽  
Brca 1 ◽  
History Of ◽  
Associated Tumors

e15165 Background: Pancreatic cancer (PC) is known to be associated with BRCA2 mutations, while the role of BRCA1 in the increase of PC risk is less evident. BRCA1/2-driven tumors, including pancreatic cancer, are sensitive to platinating agents and PARP inhibitors. Epidemiology of BRCA1 mutations in Russia is characterized by a pronounced founder effect, with the allele BRCA1 5382insC being detected in 70-90% of all BRCA1 mutation carriers. Methods: 237 patients with consecutive patients with pancreatic cancer were by questionnaires, and 149 have provided their normal DNA to the study and underwent genotyping for BRCA 1 5382insC mutations. Results: Among all the patients in 105/237 (44.3%) patients reported first-degree relatives with various types of cancer, including 11/237 (4.6%) cases of pancreatic cancer. 2/149 genotyped patients carried BRCA1 5382insC allele. Both mutation carriers had first-degree family history of breast cancer. Conclusions: Given the simplicity of founder mutation detection, BRCA1 5382insC allele deserves to be tested in Slavic pancreatic cancer, especially in those reporting family history of BRCA1-associated tumors.

Efficacy of olaparib therapy in metastatic pancreatic ductal adenocarcinoma (PDAC) with homologous recombination deficiency (HRD).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16266-e16266
Author(s):  
Elaine Tan ◽  
James Kevin Hicks ◽  
Kirsten Blue ◽  
Richard D. Kim ◽  
Estrella M. Carballido ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Maintenance Therapy ◽  
Disease Control ◽  
Retrospective Chart Review ◽  
Parp Inhibitors ◽  
Ductal Adenocarcinoma ◽  
Parp Inhibition ◽  
Brca Mutations ◽  
Exon 11

e16266 Background: Pancreatic cancer is one of the deadliest malignancies, with a 5 year OS of around 3%. Up to 3% of unselected patients (pts) with (PDAC) have the BRCA 1/2 mutation, while up to 15% possess HRD (ARID1A, ATM, BAP1, BARD1, BRIP1, CHEK1/2, FANCA, PALB2, RAD50, RAD51). PARP inhibitors, like olaparib, demonstrate clinical benefit in metastatic PDAC with BRCA mutations (mBRCA) and may have a role in those with HRD. The objective of this study is to determine the role of PARP inhibition in PDAC with HRD. Methods: This was a retrospective chart review of metastatic PDAC pts with germline (g) or somatic (s) mBRCA or HRD who received olaparib. An analysis of PFS and OS was performed for PDAC pts with mBRCA vs. HRD. Results: Forty-six pts with metastatic pancreatic cancer were identified to have mBRCA (n = 13) or HRD (n = 23) and received olaparib in our database. Median age was 73 years for mBRCA and 66 years for HRD. Five pts received olaparib as maintenance therapy after disease control with platinum: 2 mBRCA and 3 HRD pts. Six pts with mBRCA and 7 pts with HRD were platinum naïve prior to olaparib. Zero pts with mBRCA and 3 pts with HRD received olaparib after disease progression on platinum. The median (med)PFS for mBRCA vs. HRD was 6.1 months vs. 2.8 months (HR 0.5, 95% CI: 0.2-1.1, p = 0.07). The medOS for mBRCA vs. HRD was 7.7 vs. 5.3 months (HR 0.7, 95% CI: 0.2-1.9, p = 0.4). Of those with mBRCA who received olaparib, prior cisplatin exposure (n = 8) vs. cisplatin naïve (n = 5) led to medPFS of 6.1 vs. 7.8 months (HR 1.8, 95% CI 0.5-6.7, p = 0.3) and medOS of 6.8 months vs. 9.5 months (HR 1.5, 95% 0.3-6.4, p = 0.6). Six pts with HRD including gCHEK2 c.407T > C, gCHEK2 c.1461+1 G > A, gPALB2 gain (exon 11), sFANCI p.N1252S, sATM p.V2716A, sARID1A Q944fs*14 were noted to have disease control of at least 3 months on olaparib. Only one of these pts received olaparib as maintenance therapy after platinum. The medPFS was 6.1 months and medOS was not reached. One pt with HRD (sFANCI N1252S) had progressive disease on platinum prior to olaparib, but had stable disease > 5 months with olaparib. Conclusions: Our study suggests olaparib may have anticancer activity in PDAC with certain HRD. In addition, olaparib may have a role outside maintenance therapy in PDAC with mBRCA. Prospective studies are needed to confirm these findings.

scholarly journals The Role of BRCA2 Mutation Status as Diagnostic, Predictive, and Prognosis Biomarker for Pancreatic Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Javier Martinez-Useros ◽  
Jesus Garcia-Foncillas
Keyword(s):  
Pancreatic Cancer ◽  
Dna Damage ◽  
Cancer Patients ◽  
Brca2 Mutation ◽  
Acquired Resistance ◽  
Predictive Biomarker ◽  
Parp Inhibitors ◽  
Genetic Alterations ◽  
Mutation Status

Pancreatic cancer is one of the deadliest cancers worldwide, and life expectancy after diagnosis is often short. Most pancreatic tumours appear sporadically and have been highly related to habits such as cigarette smoking, high alcohol intake, high carbohydrate, and sugar consumption. Other observational studies have suggested the association between pancreatic cancer and exposure to arsenic, lead, or cadmium. Aside from these factors, chronic pancreatitis and diabetes have also come to be considered as risk factors for these kinds of tumours. Studies have found that 10% of pancreatic cancer cases arise from an inherited syndrome related to some genetic alterations. One of these alterations includes mutation inBRCA2gene.BRCA2mutations impair DNA damage response and homologous recombination by direct regulation of RAD51. In light of these findings that link genetic factors to tumour development, DNA damage agents have been proposed as target therapies for pancreatic cancer patients carryingBRCA2mutations. Some of these drugs include platinum-based agents and PARP inhibitors. However, the acquired resistance to PARP inhibitors has created a need for new chemotherapeutic strategies to targetBRCA2.The present systematic review collects and analyses the role ofBRCA2alterations to be used in early diagnosis of an inherited syndrome associated with familiar cancer and as a prognostic and predictive biomarker for the management of pancreatic cancer patients.

PET/CT IN THE DIAGNOSIS OF PANCREATIC CANCER: LITERATURE REVIEW

2018 ◽  
pp. 57-67
Author(s):  
P. E. Tulin ◽  
M. B. Dolgushin ◽  
D. I. Nevzorov ◽  
P. V. Kochergin ◽  
Yu. I. Patyutko
Keyword(s):  
Pancreatic Cancer ◽  
Literature Review ◽  
Pancreatic Neoplasms ◽  
Poor Prognosis ◽  
Modern Imaging ◽  
Pet Ct

Pancreatic cancer has a poor prognosis, often because most pancreatic neoplasms are found to be unresectable at diagnosis. Early staging of the tumor process can change the tactics of treatment and affect the survival of patients. The purpose of this review is to provide an overview of pancreatic cancer and the role of modern imaging in its diagnosis with an emphasis on PET/CT with a various radiopharmaceuticals.

Role of myeloperoxidase in relationship between smoking and risk of pancreatic cancer

2012 ◽  
Vol 32 (2) ◽  
pp. 183-185
Author(s):  
Xin-xin FU ◽  
Zhao-shen LI ◽  
Zhen-dong JIN ◽  
Hai-tao CHEN ◽  
Wei ZHU ◽  
...  
Keyword(s):  
Pancreatic Cancer

Diagnostic pancreatic cancer: the role of percutaneous biopsy and CT

2007 ◽  
Vol 31 (3) ◽  
pp. 221
Author(s):  
Z. Amin ◽  
B. Theis ◽  
R.C.G. Russell ◽  
C. House ◽  
M. Novelli ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Percutaneous Biopsy

scholarly journals A Proteomic Study on the Personalized Protein Corona of Liposomes. Relevance for Early Diagnosis of Pancreatic DUCTAL Adenocarcinoma and Biomarker Detection

2021 ◽  
Vol 2 (2) ◽  
pp. 82-93
Author(s):  
Luca Digiacomo ◽  
Francesca Giulimondi ◽  
Daniela Pozzi ◽  
Alessandro Coppola ◽  
Vincenzo La Vaccara ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Early Diagnosis ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Protein Corona ◽  
Detection Sensitivity ◽  
Ductal Adenocarcinoma ◽  
Protein Biomarkers ◽  
Ca 19.9 ◽  
Proteomic Study

Due to late diagnosis, high incidence of metastasis, and poor survival rate, pancreatic cancer is one of the most leading cause of cancer-related death. Although manifold recent efforts have been done to achieve an early diagnosis of pancreatic cancer, CA-19.9 is currently the unique biomarker that is adopted for the detection, despite its limits in terms of sensitivity and specificity. To identify potential protein biomarkers for pancreatic ductal adenocarcinoma (PDAC), we used three model liposomes as nanoplatforms that accumulate proteins from human plasma and studied the composition of this biomolecular layer, which is known as protein corona. Indeed, plasma proteins adsorb on nanoparticle surface according to their abundance and affinity to the employed nanomaterial, thus even small differences between healthy and PDAC protein expression levels can be, in principle, detected. By mass spectrometry experiments, we quantified such differences and identified possible biomarkers for PDAC. Some of them are already known to exhibit different expressions in PDAC proteomes, whereas the role of other relevant proteins is still not clear. Therefore, we predict that the employment of nanomaterials and their protein corona may represent a useful tool to amplify the detection sensitivity of cancer biomarkers, which may be used for the early diagnosis of PDAC, with clinical implication for the subsequent therapy in the context of personalized medicine.

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