&lt;p&gt;Pharmacogenomic Assessment of Patients with Colorectal Cancer and Potential Treatments&lt;/p&gt;

Bruera, Gemma; Ricevuto, Enrico

doi:10.2147/pgpm.s253586

Cited by 7 publications

(6 citation statements)

References 67 publications

(80 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the large genetic variations in drug response amongst individuals, it becomes essentially crucial to predict drug safety and efficacy and also shows the vital part PGx practice plays in the success of drug therapy [ 10 – 14 ]. PGx practice has been successfully employed in several developed countries to improve PM and advance clinical outcomes while in developing countries this has not been fully achieved yet [ 9 , 15 , 16 ]. Furthermore, there is a scarcity of PGx awareness/ knowledge in the Arab world in general [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics: Knowledge assessment amongst Syrian pharmacists and physicians

Albitar

Alchamat

2021

BMC Health Serv Res

View full text Add to dashboard Cite

Background Pharmacogenetics targets genetic variations that influence drug response. It is relatively a new science that has not been vastly employed in most developing countries including Syria. Therefore we aimed at evaluating the depth of knowledge in pharmacogenetics and the attitude towards it amongst Syrian pharmacists and physicians. Methods We carried out an internet-based questionnaire consisted of 26 questions, sent through specialized websites and private groups with a large number of pharmacists and physicians members. The survey was available online for a period of 1 month. Results The total number of respondents was 154, mostly female pharmacists. Our statistical analysis showed a strong positive association between profession (in favour of pharmacists) and pharmacogenetics knowledge p = 0.049; however, no correlation with experience p = 0.811 was found. A significant difference was reported between the knowledge of pharmacists and physicians p = 0.001 concerning drugs that need pharmacogenetics testing before being prescribed. The majority of respondents had no information about applying genetic tests in Syria before prescribing medications nor did they possess the knowledge regarding drugs that show differential responses in patients according to their unique genotypes. In our study, the percentage knowledge assessment score was low in general (mean ± Standard deviation, SD) (46% ± 13.9%). The majority of the respondents agreed that pharmacists should provide counselling to patients on the subject of pharmacogenetics. Respondents’ opinions varied concerning making pharmacogenetics learning a priority. Conclusion Lack of pharmacogenetics knowledge was found amongst respondents in general. Our findings raise concerns about the lack of awareness amongst physicians, which may hinder the implementation of this crucial field in Syria. We suggest an emphasis on the role of education, training, and conducting genotyping research on the Syrian population.

show abstract

Section: Introductionmentioning

confidence: 99%

Pharmacogenetics: Knowledge assessment amongst Syrian pharmacists and physicians

Albitar

Alchamat

2021

BMC Health Serv Res

View full text Add to dashboard Cite

show abstract

“…Granzyme B ( GZMB ) gene polymorphisms were not associated with the metastasis of CRC 33 . Studies have shown that DPYD gene polymorphisms were associated with the susceptibility to CRC 12 and the toxicity of chemotherapy drugs 34 . However, the relationship between DPYD gene polymorphisms and metastasis of CRC has not been studied.…”

Section: Discussionmentioning

confidence: 99%

Dihydropyrimidine dehydrogenase (DPYD) gene c.1627A>G A/G and G/G genotypes are risk factors for lymph node metastasis and distant metastasis of colorectal cancer

Zeng

Huang

et al. 2021

Clinical Laboratory Analysis

View full text Add to dashboard Cite

Background Dihydropyrimidine dehydrogenase (DPD) acts as the key enzyme catabolizing pyrimidines, and may affect the tumor progression. DPYD gene mutations affect DPD activity. The relationship between DPYD IVS14+1G>A, c.1627A>G, c.85T>C and lymph node metastasis (LNM) and distant metastasis (DM) of colorectal cancer (CRC) was investigated. Methods A total of 537 CRC patients were enrolled in this study. DPYD polymorphisms were analyzed by polymerase chain reaction (PCR)‐Sanger sequencing. The relationship between DPYD genotypes and clinical features of patients, metastasis of CRC was analyzed. Results About DPYD c.1627A>G, A/A (57.7%) was the most common genotype, followed by A/G (35.6%), G/G (6.7%) genotypes. In c.85T>C, T/T, T/C, and C/C genotypes are accounted for 83.6%, 16.0%, and 0.4%, respectively. Logistic regression analysis revealed that DPYD c.1627A>G A/G and G/G genotypes in the dominant model (A/G + G/G vs. A/A) were significant risk factors for the LNM (p = 0.029, OR 1.506, 95% CI = 1.048–2.165) and DM (p = 0.039, OR 1.588, 95% CI = 1.041–2.423) of CRC. In addition, DPYD c.1627A>G polymorphism was more common in patients with abnormal serum carcinoembryonic antigen (CEA) (>5 ng/ml) (p = 0.003) or carbohydrate antigen 24–2 (CA24‐2) (>20 U/ml) level (p = 0.015). Conclusions The results suggested that DPYD c.1627A>G A/G, G/G genotypes are associated with increased risk of LNM and DM of CRC.

show abstract

“…Patient experienced LTS-ms at FIr-B/FOx re-introductions, G3 diarrhea, associated with G2 asthenia, nausea, requiring irinotecan reduction, 5-fluorouracil discontinuation. Reported LTS may be favored by mutations of genes affecting fluoropyrimidine and/or irinotecan metabolism, mainly including dihydropyrimidine dehydrogenase (DPYD) and UGT1A1 genes, justifying inter-patient safety variability (20); in patients treated with triplet chemotherapy (COI regimen), plus bevacizumab or cetuximab, independent significant association with severe toxicity and treatment modifications was found for DPYD and a trend for UGT1A1*28 mutations (P=0.054) (20). In patients treated with FIr-C/FOx-C (3), reduced FUDR, UGT1A1*28, and CYP3A4 single-nucleotide polymorphisms (SNPs) were prevalently detected in patients with LTS and may predict individual LTS occurrence, specifically gastrointestinal; most patients (65%), specifically developing gastrointestinal LTS (78%), showed >1 pharmacogenomic alteration (1-3).…”

Section: Discussionmentioning

confidence: 99%

Intensive multidisciplinary treatment strategies and patient resilience to challenge long-term survival in metastatic colorectal cancer: a case report in real life and clinical practice

et al. 2021

Self Cite

View full text Add to dashboard Cite

In fit metastatic colorectal cancer (MCRC), multidisciplinary treatment strategy integrating intensive FIr-B/FOx triplet chemotherapy associated to bevacizumab and secondary metastasectomies significantly improved clinical outcomes up to progression-free survival (PFS) 17 months and overall survival (OS) 44 months. A non-elderly woman affected by rectal cancer, lymph nodes involvement, synchronous unresectable liver metastases, was treated with first-line FIr-B/FOx integrated with two-stage liver resections, short course radiotherapy, anterior rectal resection, with a PFS 9 months and progression-free interval (PFI) 4 months off-treatment. After progression characterized by single liver and lymph node inferior mesenteric axis metastases, FIr-B/FOx was re-introduced, liver and lymph node resections were performed, with a PFS 8 months and PFI 3 months. FIr-B/FOx was further proposed due to bilateral lung, and liver metastases with stable disease, PFS 8 months. Patient experienced a Limiting Toxicity Syndrome multiple sites (LTS-ms) with G3 diarrhea, G2 asthenia, nausea, requiring irinotecan reduction and 5-fluorouracil discontinuation, and subsequent oxaliplatin discontinuation, due to infusional hypersensitivity reaction. Overall, integrated first-line medical and surgical treatment strategies gained PFS 26 months. Further lines II-V of treatment obtained a combined PFS 28 months: modulated aflibercept/irinotecan, PFS 8 months; panitumumab, PFS 8 months, proposed due to KRAS/NRAS/BRAF wild-type and EGFR c.2156 G>C (p.G719A) mutation, achieving biomarkers reduction, lung, liver, lymph nodes partial responses; regorafenib, PFS 8 months; trifluridine-tipiracil, PFS 4 months and induced an LTS-ms, with febrile G4 leucopenia, G3 neutropenia, thrombocytopenia, asthenia, G2 anemia, diarrhea, hypotension. After 2 months of palliative care, patient died, at OS 58 months, gained by intensive medical/surgical treatments coupled with patient's resilience. To date, selection of tailored medical treatments, according to clinical (age, performance and comorbidity status) and molecular (RAS/BRAF and pharmacogenomic analyses) evaluations, careful monitoring of individual toxicity syndromes, potential integration of metastasectomies, and furthermore individual resilience as patient life priority need to challenge MCRC long-term survival.

show abstract

<p>Pharmacogenomic Assessment of Patients with Colorectal Cancer and Potential Treatments</p>

Cited by 7 publications

References 67 publications

Pharmacogenetics: Knowledge assessment amongst Syrian pharmacists and physicians

Pharmacogenetics: Knowledge assessment amongst Syrian pharmacists and physicians

Dihydropyrimidine dehydrogenase (DPYD) gene c.1627A>G A/G and G/G genotypes are risk factors for lymph node metastasis and distant metastasis of colorectal cancer

Intensive multidisciplinary treatment strategies and patient resilience to challenge long-term survival in metastatic colorectal cancer: a case report in real life and clinical practice

Contact Info

Product

Resources

About