Prognostication of pancreatic adenocarcinoma by expression of thymidine phosphorylase/dihydropyrimidine dehydrogenase ratio and its correlation with survival

Saif, Muhammad Wasif; Hashmi, Sharukh; Bell, Diana; Diasio, Robert B.

doi:10.1517/14740330903173217

Cited by 12 publications

(9 citation statements)

References 16 publications

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“…It important to note that no survival difference was found between TP positive and TP negative patients who had not received chemotherapy. There are other papers that have shown that TP/DPD ratio is a predictive biomarker for capecitabine in head and neck cancer [66] and pancreatic adenocarcinoma [67]. In contrast to these findings, a phase II trial found no association between TP/DPD ratio and the efficacy of concomitant chemoradiation with capecitabine in patients with pancreatic adenocarcinoma [68].…”

Section: Tp As a Predictive Biomarkermentioning

confidence: 88%

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Elamin

Rafee

Osman

et al. 2015

Cancer Microenvironment

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Thymidine phosphorylase (TP) is a nucleoside metabolism enzyme that plays an important role in the pyrimidine pathway.TP catalyzes the conversion of thymidine to thymine and 2-deoxy-α-D-ribose-1-phosphate (dRib-1-P). Although this reaction is reversible, the main metabolic function of TP is catabolic. TP is identical to the angiogenic factor platelet-derived endothelial-cell growth factor (PD-ECGF). TP is overexpressed in several human cancers in response to cellular stressful conditions like hypoxia, acidosis, chemotherapy and radiotherapy. TP has been shown to promote tumor angiogenesis, invasion, metastasis, evasion of the immuneresponse and resistance to apoptosis. Some of the biological effects of TP are dependent on its enzymatic activity, while others are mediated through cytokines like interleukin 10 (IL-10), basic fibroblast growth factor (bFGF) and tumour necrosis factor α (TNFα). Interestingly, TP also plays a role in cancer treatment through its role in the conversion of the oral fluoropyrimidine capecitabine into its active form 5-FU. TP is a predictive marker for fluoropyrimidine response. Given its various biological functions in cancer progression, TP is a promising target in cancer treatment. Further translational research is required in this area.

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Section: Tp As a Predictive Biomarkermentioning

confidence: 88%

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Elamin

Rafee

Osman

et al. 2015

Cancer Microenvironment

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“…With regards to cardiotoxicity, it has been long recognized than 5FU causes cardiac toxicity 60 . However, the syndrome of 5FU -associated cardiotoxicity remains poorly defined and its incidence may be underestimated.…”

Section: Tolerabilitymentioning

confidence: 99%

“…However, the syndrome of 5FU -associated cardiotoxicity remains poorly defined and its incidence may be underestimated. Large series suggest that clinically demonstrated 5FU-related cardiotoxicity ranges from 1.6 to 4% 60 .…”

Section: Tolerabilitymentioning

confidence: 99%

From First Line to Sequential Treatment in the Management of Metastatic Pancreatic Cancer

et al. 2018

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The current management of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is based on systemic chemotherapy. The results of the MPACT and PRODIGE clinical trials have demonstrated that the combination of nab-paclitaxel and gemcitabine (GEM) as well as FOLFIRINOX regimen result in improvement in overall survival when compared to GEM alone. Treatment guidelines now recommend either one of these two regimens as first line treatment for fit patients with mPDAC. Because no head-to-head comparison between the two regimens exists, the selection of one versus the other is based on clinical criteria. The design and eligibility criteria of these two clinical trials are dissimilar, making the results of the MPACT trial more applicable to the general population of patients with mPDAC. In addition, the combination of nab-paclitaxel and GEM is better tolerated and easier to administer in clinical practice than FOLFIRINOX. Furthermore, when the regimens are studied in comparable patient populations the efficacy results are very similar. Nanoliposomal irinotecan plus 5FU has recently demonstrated a significant increase in efficacy rates after a GEM-based treatment. Importantly, treatment of mPDAC should now be considered as a continuum care for patients who are fit, with second and even third line treatments. Different sequential treatment algorithms are proposed based on available data. In retrospective studies, patients who were managed with GEM-based regimens followed by fluoropyrimidine-based regimens appear to have the most favorable outcome.

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“…TP/DPD ratio seems to correlate positively with the efficacy of capecitabine in human xenograft models. Saif et al demonstrated in a study that a lower TP/DPD was associated with a survival benefit of 4 months [ 57 ]. This looks small, but we must take into account that the 5-year survival is less than 5%.…”

Section: Genetic Factors Affecting Outcomementioning

confidence: 99%

Genetic factors affecting patient responses to pancreatic cancer treatment

Fotopoulos

Syrigos

Saif

2016

aog

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Cancer of the exocrine pancreas is a malignancy with a high lethal rate. Surgical resection is the only possible curative mode of treatment. Metastatic pancreatic cancer is incurable with modest results from the current treatment options. New genomic information could prove treatment efficacy. An independent review of PubMed and ScienceDirect databases was performed up to March 2016, using combinations of terms such pancreatic exocrine cancer, chemotherapy, genomic profile, pancreatic cancer pharmacogenomics, genomics, molecular pancreatic pathogenesis, and targeted therapy. Recent genetic studies have identified new markers and therapeutic targets. Our current knowledge of pancreatic cancer genetics must be further advanced to elucidate the molecular basis and pathogenesis of the disease, improve the accuracy of diagnosis, and guide tailor-made therapies.

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Prognostication of pancreatic adenocarcinoma by expression of thymidine phosphorylase/dihydropyrimidine dehydrogenase ratio and its correlation with survival

Cited by 12 publications

References 16 publications

Thymidine Phosphorylase in Cancer; Enemy or Friend?

Thymidine Phosphorylase in Cancer; Enemy or Friend?

From First Line to Sequential Treatment in the Management of Metastatic Pancreatic Cancer

Genetic factors affecting patient responses to pancreatic cancer treatment

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