BRCA in Gastrointestinal Cancers: Current Treatments and Future Perspectives

A strong association between pancreatic cancer and BRCA1 and BRCA2 mutations is documented. Based on promising results of breast and ovarian cancers, several clinical trials with poly (ADP-ribose) polymerase inhibitors (PARPi) are ongoing for gastrointestinal (GI) malignancies, especially for pancreatic cancer. Indeed, the POLO trial results provide promising and awaited changes for the pancreatic cancer therapeutic landscape. Contrariwise, for other gastrointestinal tumors, the rationale is currently only alleged. The role of BRCA mutation in gastrointestinal cancers is the subject of this review. In particular, we aim to provide the latest updates about novel therapeutic strategies that, exploiting DNA repair defects, promise to shape the future therapeutic scenario of GI cancers.

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Role of BRCA1 and BRCA2 mutations in pancreatic cancer

Gut ◽

10.1136/gut.2006.101220 ◽

2007 ◽

Vol 56 (5) ◽

pp. 601-605 ◽

Cited By ~ 58

Author(s):

J. B Greer ◽

D. C Whitcomb

Keyword(s):

Pancreatic Cancer ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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Oncogenic Role of Exosomal Circular and Long Noncoding RNAs in Gastrointestinal Cancers

International Journal of Molecular Sciences ◽

10.3390/ijms23020930 ◽

2022 ◽

Vol 23 (2) ◽

pp. 930

Author(s):

Ba Da Yun ◽

Ye Ji Choi ◽

Seung Wan Son ◽

Gabriel Adelman Cipolla ◽

Fernanda Costa Brandão Berti ◽

...

Keyword(s):

Epithelial To Mesenchymal Transition ◽

Cell Communication ◽

Noncoding Rnas ◽

Long Noncoding Rnas ◽

Circular Rnas ◽

Gastrointestinal Cancers ◽

Gastrointestinal Malignancies ◽

Mesenchymal Transition ◽

Novel Therapeutic Strategies

Circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs) are differentially expressed in gastrointestinal cancers. These noncoding RNAs (ncRNAs) regulate a variety of cellular activities by physically interacting with microRNAs and proteins and altering their activity. It has also been suggested that exosomes encapsulate circRNAs and lncRNAs in cancer cells. Exosomes are then discharged into the extracellular environment, where they are taken up by other cells. As a result, exosomal ncRNA cargo is critical for cell–cell communication within the cancer microenvironment. Exosomal ncRNAs can regulate a range of events, such as angiogenesis, metastasis, immune evasion, drug resistance, and epithelial-to-mesenchymal transition. To set the groundwork for developing novel therapeutic strategies against gastrointestinal malignancies, a thorough understanding of circRNAs and lncRNAs is required. In this review, we discuss the function and intrinsic features of oncogenic circRNAs and lncRNAs that are enriched within exosomes.

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MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

Genes ◽

10.3390/genes10100752 ◽

2019 ◽

Vol 10 (10) ◽

pp. 752 ◽

Cited By ~ 11

Author(s):

Rawat ◽

Kadian ◽

Gupta ◽

Kumar ◽

Chain ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cancer Patients ◽

Therapeutic Potential ◽

Critical Role ◽

Mirna Biogenesis ◽

Effective Management ◽

Future Directions ◽

Novel Therapeutic Strategies ◽

Conclusion Section

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.

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Factors influencing women’s decisions to getting tested for BRCA mutation

Journal of Nursing Education and Practice ◽

10.5430/jnep.v9n3p33 ◽

2018 ◽

Vol 9 (3) ◽

pp. 33 ◽

Cited By ~ 1

Author(s):

Suha Al-Oballi Kridli ◽

Holly Austin

Keyword(s):

Ovarian Cancer ◽

Brca Mutation ◽

Genetic Mutations ◽

Inclusion Criteria ◽

Breast And Ovarian Cancer ◽

Brca1 And Brca2 ◽

Brca Mutations ◽

Factors Influencing ◽

Brca1 And Brca2 Mutations ◽

Internal And External Factors

Ovarian cancer is the leading cause of death among gynecological cancers. There are many risk factors that can increase a woman’s susceptibility to breast and ovarian cancers, some of which are modifiable. However, non-modifiable risks for breast and ovarian cancer include the presence of genetic mutations (BRCA) increase the risk of these diseases. The purpose of this review was to identify factors, reported in the literature, known to affect women’s decision to get genetic testing for BRCA1 and BRCA2 mutations for hereditary breast and ovarian cancer. A total of 31 studies that met the inclusion criteria were included in this review. Several internal and external factors, influencing women’s decision to getting tested for BRCA mutations, were identified and explained. Implications for clinical practice were provided.

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Prevalence of BRCA1 and BRCA2 Mutations Among High-Risk Saudi Patients With Breast Cancer

Journal of Global Oncology ◽

10.1200/jgo.18.00066 ◽

2018 ◽

pp. JGO.18.00066 ◽

Cited By ~ 1

Author(s):

Omalkhair Abulkhair ◽

Mohammed Al Balwi ◽

Ola Makram ◽

Lamia Alsubaie ◽

Medhat Faris ◽

...

Keyword(s):

Breast Cancer ◽

High Risk ◽

Novel Mutation ◽

Brca Mutation ◽

Brca1 Gene ◽

Brca1 And Brca2 ◽

Brca1 Mutations ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations ◽

Saudi Patients

Purpose Over the past three decades, the incidence rate of breast cancer (BC) among Arab women has continually increased. However, data on the prevalence of BRCA1/2 mutations are scarce. Although the population in Saudi Arabia is at large homogeneous and consanguinity is common, especially in the central, eastern, and southern regions of the country, the prevalence of BRCA1 and BRCA2 mutations and the characteristics of BC are not well studied in the country. Methods This prospective observational study intended to determine the prevalence of BRCA1 and BRCA2 mutations and sought to examine the clinicopathologic features of BC associated with these mutations. Results Of 310 patients, 270 (87%) had no mutation. BRCA mutations were identified in 40 patients; BRCA1 mutations were found in 11% of patients, and BRCA2 mutations were found in 2% of patients. Variants of unknown significance were found in 15% of patients (45 patients). Triple-negative BC (TNBC) accounted for 86% of all patients with BC and mutations. The following three recurrent deleterious founder BRCA1 mutations were observed: c.4136_4137delCT was observed in five unrelated patients, c.5530delC was observed in three unrelated patients, and c.4524G>A mutations were observed in five unrelated patients. One novel mutation was identified in the BRCA1 gene (c.5512 dup [p.Glu1838Glyfs*42]). Conclusion Among high-risk Saudi patients with BC, BRCA1 mutations are prevalent (11%). TNBC is the most common BC subtype. Furthermore, age alone does not have a significant association with mutation, but a combination of risk factors such as age, familial history, and TNBC has a significant association with BRCA mutation.

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Prevalence and characteristics of pancreatic cancer in families with BRCA1 and BRCA2 mutations

Familial Cancer ◽

10.1007/s10689-008-9220-x ◽

2008 ◽

Vol 8 (2) ◽

pp. 153-158 ◽

Cited By ~ 23

Author(s):

Daniel H. Kim ◽

Beth Crawford ◽

John Ziegler ◽

Mary S. Beattie

Keyword(s):

Pancreatic Cancer ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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Expert Guidance on Screening for Colorectal and Pancreatic Cancer in Carriers of BRCA1 and BRCA2 Mutations

Default Digital Object Group ◽

10.1200/adn.20.200361 ◽

2020 ◽

Keyword(s):

Pancreatic Cancer ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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BRCA1 and BRCA2 mutations sensitize to chemotherapy in patient-derived pancreatic cancer xenografts

British Journal of Cancer ◽

10.1038/bjc.2015.220 ◽

2015 ◽

Vol 113 (3) ◽

pp. 425-432 ◽

Cited By ~ 42

Author(s):

I Lohse ◽

A Borgida ◽

P Cao ◽

M Cheung ◽

M Pintilie ◽

...

Keyword(s):

Pancreatic Cancer ◽

Brca1 And Brca2 ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

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Germline Genetic Variation, Cancer Outcome, and Pharmacogenetics

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.2336 ◽

2010 ◽

Vol 28 (26) ◽

pp. 4029-4037 ◽

Cited By ~ 44

Author(s):

Linda Coate ◽

Sinead Cuffe ◽

Anne Horgan ◽

Rayjean J. Hung ◽

David Christiani ◽

...

Keyword(s):

Genetic Variation ◽

Cancer Prognosis ◽

Cancer Syndrome ◽

Brca1 And Brca2 ◽

Biologic Drugs ◽

Cancer Outcome ◽

Tamoxifen Efficacy ◽

Brca1 And Brca2 Mutations ◽

The Impact

Studies of the role of germline or inherited genetic variation on cancer outcome can fall into three distinct categories. First, the impact of highly penetrant but lowly prevalent mutations of germline DNA on cancer prognosis has been studied extensively for BRCA1 and BRCA2 mutations as well as mutations related to hereditary nonpolyposis colorectal cancer syndrome. These mainly modest-sized analyses have produced conflicting results. Although some associations have been observed, they may not be independent of other known clinical or molecular prognostic factors. Second, the impact of germline polymorphisms on cancer prognosis is a burgeoning field of research. However, a deeper understanding of potentially confounding somatic changes and larger multi-institutional, multistage studies may be needed before consistent results are seen. Third, research examining the impact of germline genetic variation on differential treatment response or toxicity (pharmacogenetics) has produced some proof-of-principle results. Putative germline pharmacogenetic predictors of outcome include DPYD polymorphisms and fluorouracil toxicity, UGT1A1 variation and irinotecan toxicity, and CYP2D6 polymorphisms and tamoxifen efficacy, with emerging data on predictors of molecularly targeted or biologic drugs. Here we review data pertaining to these germline outcome and germline toxicity relationships.

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