Pub Date : 2022-09-28DOI: 10.2174/1573394718666220928152207
E. Bali
In this study, it was aimed to evaluate the research articles indexed on the Web of Science about drug repurposing in cancer between 2012 and November 2021. Findings were obtained from the Web of Science database. A bibliometric method was performed to analyze publication types, research fields, citations, countries, institutions, active journals, authors, and keywords. The data was supported by using collaboration networks including visualization maps. Globally, of the 5.568 publications, only 408 were research papers in cancer research. However, the number of publications and citations was observed to increase significantly over the years, especially in 2020 and 2021. The majority of the publication types were original articles in the oncology field. Unsurprisingly, the USA was the most active country in publishing articles. The University of Texas in the USA was the institution with the highest number of publications. A team of researchers led by Zdenek Skrott published the most cited paper. While Pantziarka’s research team was the most active authors in publication productivity, Ferlay J’s research group had the highest value of citation burst. Cancers and Cancers Research were the most active journals in terms of publications and citations numbers, respectively. After the keyword drug repurposing, the most frequently used keywords were “apoptosis” and “breast cancer”, indicating the research hotspots. This is the first bibliometric research in detail to point out that drug repurposing in cancer is a novel and growing area, especially in developed countries.
{"title":"Drug repurposing in cancer research: A Bibliometric analysis from 2012 to 2021","authors":"E. Bali","doi":"10.2174/1573394718666220928152207","DOIUrl":"https://doi.org/10.2174/1573394718666220928152207","url":null,"abstract":"\u0000\u0000In this study, it was aimed to evaluate the research articles indexed on the Web of Science about drug repurposing in cancer between 2012 and November 2021.\u0000\u0000\u0000\u0000Findings were obtained from the Web of Science database. A bibliometric method was performed to analyze publication types, research fields, citations, countries, institutions, active journals, authors, and keywords. The data was supported by using collaboration networks including visualization maps. Globally, of the 5.568 publications, only 408 were research papers in cancer research. However, the number of publications and citations was observed to increase significantly over the years, especially in 2020 and 2021. The majority of the publication types were original articles in the oncology field. Unsurprisingly, the USA was the most active country in publishing articles.\u0000\u0000\u0000\u0000The University of Texas in the USA was the institution with the highest number of publications. A team of researchers led by Zdenek Skrott published the most cited paper. While Pantziarka’s research team was the most active authors in publication productivity, Ferlay J’s research group had the highest value of citation burst. Cancers and Cancers Research were the most active journals in terms of publications and citations numbers, respectively. After the keyword drug repurposing, the most frequently used keywords were “apoptosis” and “breast cancer”, indicating the research hotspots.\u0000\u0000\u0000\u0000This is the first bibliometric research in detail to point out that drug repurposing in cancer is a novel and growing area, especially in developed countries.\u0000","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45610328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-27DOI: 10.2174/1573394718666220927103028
I. Panfoli
{"title":"Polyphenols in anti-cancer therapy and prevention: should we add the FoF1-ATP Synthase Inhibition?","authors":"I. Panfoli","doi":"10.2174/1573394718666220927103028","DOIUrl":"https://doi.org/10.2174/1573394718666220927103028","url":null,"abstract":"<jats:sec>\u0000<jats:title />\u0000<jats:p />\u0000</jats:sec>","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48387502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-15DOI: 10.2174/1573394718666220915114659
F. Kazemi, Maryam Fasihi-karami, Reza Afrisham, S. Karami, Ehsan Beigzadeh
It has been reported that more than 20% of malignancies in the developing countries are induced by some infections. However, helminth infections related to malignancies have been less appreciated. Since, helminths sometimes infect their hosts for over decades, the host’s immune responses get modulated Several studies have shown that there are many similarities between the persistence of parasite infection and progression of tumors in terms of biochemical and immune responses. Thus, this review was designed to evaluate the association between some helminths and tumorigenesis through immunological and biochemical factors. The results of the current study showed that helminth infections could be implicated in the pathogenesis of some cancers. Several factors contribute to tumorigenesis of these helminth-stimulated tumors. These helminth infections increase the proportions of CD19+ B cells and F4/80+ macrophages as well as reduce the proportions of CD8+ lymphocytes, and increase the levels of VEGF, IL-10, and IL-4. In addition, this parasite-stimulated inflammation may encourage neoplasia. Also, catechol-estrogens and oxysterols related to some helminths can play a key role in tumorigenesis. Thus, the effects of parasitic helminth infections on the development of tumor is very important. However, the investigation on these issues requires further study, which can be helpful in preventing parasitic helminth infections-related cancers.
{"title":"Association between some helminths and tumorigenesis through immunological and biochemical factors","authors":"F. Kazemi, Maryam Fasihi-karami, Reza Afrisham, S. Karami, Ehsan Beigzadeh","doi":"10.2174/1573394718666220915114659","DOIUrl":"https://doi.org/10.2174/1573394718666220915114659","url":null,"abstract":"\u0000\u0000It has been reported that more than 20% of malignancies in the developing countries are induced by some infections. However, helminth infections related to malignancies have been less appreciated. Since, helminths sometimes infect their hosts for over decades, the host’s immune responses get modulated Several studies have shown that there are many similarities between the persistence of parasite infection and progression of tumors in terms of biochemical and immune responses. Thus, this review was designed to evaluate the association between some helminths and tumorigenesis through immunological and biochemical factors. The results of the current study showed that helminth infections could be implicated in the pathogenesis of some cancers. Several factors contribute to tumorigenesis of these helminth-stimulated tumors. These helminth infections increase the proportions of CD19+ B cells and F4/80+ macrophages as well as reduce the proportions of CD8+ lymphocytes, and increase the levels of VEGF, IL-10, and IL-4. In addition, this parasite-stimulated inflammation may encourage neoplasia. Also, catechol-estrogens and oxysterols related to some helminths can play a key role in tumorigenesis. Thus, the effects of parasitic helminth infections on the development of tumor is very important. However, the investigation on these issues requires further study, which can be helpful in preventing parasitic helminth infections-related cancers.\u0000","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42949605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-29DOI: 10.2174/1573394718666220829125338
Yusmazura Zakaria, Nur Fatin Najihah Marzuki
Immunotherapy has garnered attention in cancer treatment following the success of recent trials in solid tumors adopting PD-L1/PD-1 checkpoint inhibition. PD-1 is a T-cell checkpoint molecule that limits autoimmune and auto-inflammatory reactivity in the normal host by suppressing adaptive immune responses. Although PD-L1 expression in the tumor is generally considered a poor prognostic marker, it has been used to screen patients for cancer therapy since it is associated with a positive response to PD-L1/PD-1 blocking antibodies. This review focuses on the complex interconnections between cancer-reactive and self-reactive immune cells, as well as the potential contribution of a wide range of leading immunomodulatory chemical products from plant-based origins as cancer therapeutics or to foreseeably ameliorate autoimmune diseases. The natural compounds derived from plants should be used as a PD-L1/PD-1 checkpoint modulator to combat cancer cells and other chronic diseases. The significance of herbal plant extracts in the regulation of the PD-L1/PD-1 checkpoint is presented in this review together with the expression of PD-L1 and PD-1 in cancer cells and diseases in human bodies.
{"title":"Medicinal Plants in The Regulation of PD-L1/PD-1 Immune Checkpoint of Various Human Cancer Cells: A Narrative Review","authors":"Yusmazura Zakaria, Nur Fatin Najihah Marzuki","doi":"10.2174/1573394718666220829125338","DOIUrl":"https://doi.org/10.2174/1573394718666220829125338","url":null,"abstract":"\u0000\u0000Immunotherapy has garnered attention in cancer treatment following the success of recent trials in solid tumors adopting PD-L1/PD-1 checkpoint inhibition. PD-1 is a T-cell checkpoint molecule that limits autoimmune and auto-inflammatory reactivity in the normal host by suppressing adaptive immune responses. Although PD-L1 expression in the tumor is generally considered a poor prognostic marker, it has been used to screen patients for cancer therapy since it is associated with a positive response to PD-L1/PD-1 blocking antibodies.\u0000\u0000\u0000\u0000This review focuses on the complex interconnections between cancer-reactive and self-reactive immune cells, as well as the potential contribution of a wide range of leading immunomodulatory chemical products from plant-based origins as cancer therapeutics or to foreseeably ameliorate autoimmune diseases. The natural compounds derived from plants should be used as a PD-L1/PD-1 checkpoint modulator to combat cancer cells and other chronic diseases.\u0000\u0000\u0000\u0000The significance of herbal plant extracts in the regulation of the PD-L1/PD-1 checkpoint is presented in this review together with the expression of PD-L1 and PD-1 in cancer cells and diseases in human bodies.\u0000","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41359459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-29DOI: 10.2174/1573394718666220829122410
S. Abd-Elsalam, Hatem Samir Abd El-Rauf, M. Y. Soliman, Ahmed M. Gad, Eid Abdel-Monsef Abou-Omar, M. Saleh, R. Abdellatif, Amina Fouad, Omar Mahmoud Azzam, Y. Abo-Amer
Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Indeed, we need a novel tumor marker other than AFP for early detection and to improve the outcome. Serum thioredoxin is a promising protein involved in pathogenesis in many malignancies. The study aims to evaluate serum thioredoxin and its gene polymorphism in HCC in cirrhotic patients due to HCV infection. 350 patients with HCC, 350 patients with chronic liver diseases, and 300 healthy controls were enrolled in our study. Serum thioredoxin level was measured by ELISA and molecular study of thioredoxin domain-containing 5 (TXNDC5) gene polymorphism (rs1225943) polymorphism using real-time polymerase chain reaction by Taqman allele discrimination was done for all subjects. Our study revealed a significant increase in serum thioredoxin levels in patients with HCC compared to chronic liver diseases and healthy controls. Using Receiver operating characteristic (ROC) curve at the area under the curve (AUC) 0.917 and cut-off value of >14.6 U/ml, our overall sensitivity and specificity for HCC group over the other groups were 86 % and 92.15% respectively with 92.2% positive predictive value and 54.9% negative predictive value. The molecular study of TXNDC5 gene polymorphism (rs1225943) polymorphism revealed no significant difference between the studied groups. Serum thioredoxin may be used as a promising tumor marker for HCC. Future researches are needed to assess its use as a single or combined with other markers in the diagnosis and follow-up of the patients after interventions.
{"title":"The value of thioredoxin level and its gene Polymorphism in diagnosis of post- HCV Hepatocellular Carcinoma","authors":"S. Abd-Elsalam, Hatem Samir Abd El-Rauf, M. Y. Soliman, Ahmed M. Gad, Eid Abdel-Monsef Abou-Omar, M. Saleh, R. Abdellatif, Amina Fouad, Omar Mahmoud Azzam, Y. Abo-Amer","doi":"10.2174/1573394718666220829122410","DOIUrl":"https://doi.org/10.2174/1573394718666220829122410","url":null,"abstract":"\u0000\u0000Hepatocellular carcinoma (HCC) is one of the most common malignancies and a leading cause of cancer-related death worldwide. Indeed, we need a novel tumor marker other than AFP for early detection and to improve the outcome. Serum thioredoxin is a promising protein involved in pathogenesis in many malignancies. The study aims to evaluate serum thioredoxin and its gene polymorphism in HCC in cirrhotic patients due to HCV infection.\u0000\u0000\u0000\u0000350 patients with HCC, 350 patients with chronic liver diseases, and 300 healthy controls were enrolled in our study. Serum thioredoxin level was measured by ELISA and molecular study of thioredoxin domain-containing 5 (TXNDC5) gene polymorphism (rs1225943) polymorphism using real-time polymerase chain reaction by Taqman allele discrimination was done for all subjects.\u0000\u0000\u0000\u0000Our study revealed a significant increase in serum thioredoxin levels in patients with HCC compared to chronic liver diseases and healthy controls. Using Receiver operating characteristic (ROC) curve at the area under the curve (AUC) 0.917 and cut-off value of >14.6 U/ml, our overall sensitivity and specificity for HCC group over the other groups were 86 % and 92.15% respectively with 92.2% positive predictive value and 54.9% negative predictive value. The molecular study of TXNDC5 gene polymorphism (rs1225943) polymorphism revealed no significant difference between the studied groups.\u0000\u0000\u0000\u0000Serum thioredoxin may be used as a promising tumor marker for HCC. Future researches are needed to assess its use as a single or combined with other markers in the diagnosis and follow-up of the patients after interventions.\u0000","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42290048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-26DOI: 10.2174/1573394718666220826153144
Priya Chikara, A. Deep, Nitin Bansal, Sanjiv Kumar, Sandeep Bansal, Arun Sharma, I. Singh, R. Marwaha
Agave angustifolia Haw. is a commercial crop grown in the highlands of Oaxaca State (Southern Mexico), a semi-arid region that belongs to the Agavaceae family, and it contains a variety of bioactive compounds that are linked to various biological activities The purpose of this study was to assess the antioxidant and anticancer potential of Agave angustifolia extract (AAE). AAE contained phenolic compounds, saponins, and fatty acids, which are responsible for antioxidant and anticancer activity, according to the GCMS analysis AAE exhibited antioxidant activity based on Hydrogen peroxide scavenging assays (IC50 value of 203.00 µg/ml) and anticancer activity (IC50 value of 82.70±1.458 μg/ml) compared with standard drug (Doxorubicin) which shows lower inhibitory rate than Extract against HeLa CCL-2 cancer cell line. In this study, the chemical constituents and biological properties of AAE were determined.
{"title":"Phytochemical screening and biological potentials of Agave angustifolia Haw. leaves extract as antioxidant and anticancer agents","authors":"Priya Chikara, A. Deep, Nitin Bansal, Sanjiv Kumar, Sandeep Bansal, Arun Sharma, I. Singh, R. Marwaha","doi":"10.2174/1573394718666220826153144","DOIUrl":"https://doi.org/10.2174/1573394718666220826153144","url":null,"abstract":"\u0000\u0000Agave angustifolia Haw. is a commercial crop grown in the highlands of Oaxaca State (Southern Mexico), a semi-arid region that belongs to the Agavaceae family, and it contains a variety of bioactive compounds that are linked to various biological activities\u0000\u0000\u0000\u0000The purpose of this study was to assess the antioxidant and anticancer potential of Agave angustifolia extract (AAE). AAE contained phenolic compounds, saponins, and fatty acids, which are responsible for antioxidant and anticancer activity, according to the GCMS analysis\u0000\u0000\u0000\u0000AAE exhibited antioxidant activity based on Hydrogen peroxide scavenging assays (IC50 value of 203.00 µg/ml) and anticancer activity (IC50 value of 82.70±1.458 μg/ml) compared with standard drug (Doxorubicin) which shows lower inhibitory rate than Extract against HeLa CCL-2 cancer cell line.\u0000\u0000\u0000\u0000In this study, the chemical constituents and biological properties of AAE were determined.\u0000","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46118890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-23DOI: 10.2174/1573394718666220823154459
K. Palaniappan
The field of oncotherapy has always been looking out for alternative treatment methods that have much lesser side effects compared to the currently used therapies that lower down the patients’ quality of life. Gold Nanoparticle [GNP]-mediated photothermal therapies are proving to be a boon as they are both non-invasive and tumour-specific. This review analyses how GNPs can help right from the beginning, that is, the diagnosis of cancer, to the end, that is, effective ablation of cancerous cells. Their ability to function as photothermal absorbers, targeted drug deliverers, and inducers of photoimmunity are reviewed in detail, bringing out the current clinical progress in each of those areas. Even though they stand to be a promising solution for cancer therapy, it is necessary to understand their biodegradation and in vivo toxicity before their extensive clinical usage.
{"title":"Clinical progress in gold nanoparticle (GNP)-mediated photothermal cancer therapy.","authors":"K. Palaniappan","doi":"10.2174/1573394718666220823154459","DOIUrl":"https://doi.org/10.2174/1573394718666220823154459","url":null,"abstract":"\u0000\u0000The field of oncotherapy has always been looking out for alternative treatment methods that have much lesser side effects compared to the currently used therapies that lower down the patients’ quality of life. Gold Nanoparticle [GNP]-mediated photothermal therapies are proving to be a boon as they are both non-invasive and tumour-specific. This review analyses how GNPs can help right from the beginning, that is, the diagnosis of cancer, to the end, that is, effective ablation of cancerous cells. Their ability to function as photothermal absorbers, targeted drug deliverers, and inducers of photoimmunity are reviewed in detail, bringing out the current clinical progress in each of those areas. Even though they stand to be a promising solution for cancer therapy, it is necessary to understand their biodegradation and in vivo toxicity before their extensive clinical usage.\u0000","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47104751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-20DOI: 10.2174/1573394718666220820114240
Ayushi Singh, Rakhi Mishra, A. Mazumder, R. Mazumder, P. Tiwari
Significant progress in the field of anticancer research has led to a rise in the study of bioactive chemicals with potential anticancer effects. Still, many bioactive natural chemicals must be investigated in order to generate more effective anti-cancer therapeutics. There have been many attempts to treat cancer, and this review summarizes many bioactive substances obtained from nature that have the ability to fight against different types of malignancies with minimal harm, based on diverse research. Polyphenolic flavonoids, carotenoid (fucoxanthin), tannin, and other notable natural bioactive with anticancer potential were examined and reviewed systematically with an eye toward their significance in many types of cancer treatment. Throughout the text, it was concluded that the natural bioactive play a very prominent role in combating different types of cancer, and the information related to the bioactive role in cancer treatment over the last 10 years was gathered from several research and review articles. The material kept in this paper can act as a template for future research in expressing the more beneficial role of other bioactive in acting as an adjuvant in chemotherapy practice for prevention and treatment of various cancer additionally with no or minimal adverse effects which are prominent with the conventional drugs used for the treatment of cancer.
{"title":"Multiple Cancer Combating by Natural Bioactives: A Review","authors":"Ayushi Singh, Rakhi Mishra, A. Mazumder, R. Mazumder, P. Tiwari","doi":"10.2174/1573394718666220820114240","DOIUrl":"https://doi.org/10.2174/1573394718666220820114240","url":null,"abstract":"\u0000\u0000Significant progress in the field of anticancer research has led to a rise in the study of bioactive chemicals with potential anticancer effects. Still, many bioactive natural chemicals must be investigated in order to generate more effective anti-cancer therapeutics.\u0000\u0000\u0000\u0000There have been many attempts to treat cancer, and this review summarizes many bioactive substances obtained from nature that have the ability to fight against different types of malignancies with minimal harm, based on diverse research. Polyphenolic flavonoids, carotenoid (fucoxanthin), tannin, and other notable natural bioactive with anticancer potential were examined and reviewed systematically with an eye toward their significance in many types of cancer treatment.\u0000\u0000\u0000\u0000Throughout the text, it was concluded that the natural bioactive play a very prominent role in combating different types of cancer, and the information related to the bioactive role in cancer treatment over the last 10 years was gathered from several research and review articles. The material kept in this paper can act as a template for future research in expressing the more beneficial role of other bioactive in acting as an adjuvant in chemotherapy practice for prevention and treatment of various cancer additionally with no or minimal adverse effects which are prominent with the conventional drugs used for the treatment of cancer.\u0000","PeriodicalId":43754,"journal":{"name":"Current Cancer Therapy Reviews","volume":" ","pages":""},"PeriodicalIF":0.6,"publicationDate":"2022-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45240973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-03DOI: 10.2174/1573394718666220803100928
Khalid Zouine, Meryem Abassi, L. Bouguenouch, Ismail Mouhrach, Kettani Oussama, Souleimani Abdellah, Ouldim Karim, M. Nawfel
The pharmacogenetics of anticancer drugs is of paramount importance in minimizing their side effects and increasin their efficacy. When applied to capecitabine, the result is that variation in patient responses has been largely linked to different genetic polymorphisms of dihydropyrimidine dehydrogenase (DPD) and this variation explains in many cases the onset of toxicity of this medication in patients. Failure of this enzyme is known to be responsible for a high incidence of serious or even fatal side effects. In this study conducted on Moroccan patients under treatment with capecitabine at usual doses at the Fez University Hospital, the first in Africa and Morocco, we are looking for the presence of four variants of DPD gene (DPYD): T486A on exon 5 (rs666523971), c.1679T> G (p.I560S; rs55886062; allele DPYD * 13) on exon 13, c.1905 + 1G> A (IVS14 + 1G> A; rs3918290; allele DPYD * 2A) on the splice site near exon 14 and the c.2846A> T mutation (p.D949V; rs67376798) on exon 22. We will therefore seek to establish the cause-and-effect relationship between this toxicity and the presence of these variants in his patients, which will allow us to avoid the dangerous prescription of capecitabine in patients carrying these polymorphisms. This is a prospective study which is carried out at the Laboratory of Medical Genetics of the CHU Hassan II Fez and spread over a period of 3 years. Patient recruitment was carried out from the oncology department of CHU Hassan II-Fès. All recruited patients are treated with capecitabine A total of 64 patients were tested. Blood samples (5 ml) were obtained from each one of them after their consent and DNA was extracted. The study of these four polymorphisms was carried out by PCR sequencing. We have studied 64 patients taking capecitabine. Their median age was 50 years and the mean age of 50,79 years with extremes of 25 and 78 years. The sex ratio F / M was 0,60. Different levels of toxicity have been developed in patients ranging from simple vomiting to IV degree hand and foot syndrome and second degree neuropathy involving total discontinuation of treatment. These mutations were not found in the patients. Thus it would be interesting to enlarge the sample size, to look for these polymorphisms and others on other exons of the DPYD gene and to try to understand the cause of this increased incidence of capecitabine toxicity in the Moroccan population. Capecitabine-based chemotherapy caused adverse effects with varying levels in its patients. The SNPs on the DPYD gene sought were not found in this Moroccan sample. It is desirable to screen more patients and to search for other SNPs to understand the toxicity of capecitabine in relation to the DPYD gene. This will make it possible to adjust the dosage of this drug, increase its effectiveness and minimize its toxicity.
抗癌药物的药物遗传学对减少其副作用和提高其疗效至关重要。当应用于卡培他滨时，结果是患者反应的变化在很大程度上与二氢嘧啶脱氢酶(DPD)的不同遗传多态性有关，这种变异在许多情况下解释了该药物在患者中的毒性发作。众所周知，这种酶的失效是造成严重甚至致命副作用的原因。在非斯大学医院(Fez University Hospital)对接受卡培他滨常规剂量治疗的摩洛哥患者进行的这项研究中，我们正在寻找DPD基因(DPYD)的四种变体的存在:外显子5上的T486A (rs666523971)， c.1679T> G (p.I560S;rs55886062;外显子13的等位基因DPYD * 13, c.1905 + 1G> A (IVS14 + 1G> A);rs3918290;等位基因DPYD * 2A)和c.2846A> T突变(p.D949V;Rs67376798)外显子22。因此，我们将寻求建立这种毒性与他的患者中这些变异的存在之间的因果关系，这将使我们能够避免对携带这些多态性的患者使用卡培他滨的危险处方。这是在朱哈桑二世非斯医学遗传学实验室进行的一项前瞻性研究，为期3年。患者招募从CHU Hassan ii - f的肿瘤科进行。所有招募的患者都接受卡培他滨治疗，总共64名患者接受了测试。经同意后，每人抽取血液样本(5ml)并提取DNA。对这4个多态性进行PCR测序研究。我们研究了64例服用卡培他滨的患者。他们的中位年龄为50岁，平均年龄为50岁，79岁，极端年龄为25岁和78岁。性别比F / M为0.60。不同程度的毒性已在患者中发展，从单纯呕吐到IV度手足综合征和涉及完全停止治疗的二度神经病变。这些突变在患者中未被发现。因此，扩大样本量，在DPYD基因的其他外显子上寻找这些多态性和其他多态性，并试图了解摩洛哥人群中卡培他滨毒性发生率增加的原因，将是很有趣的。以卡培他滨为基础的化疗在患者中引起不同程度的不良反应。在这个摩洛哥样本中没有发现DPYD基因上的snp。希望筛选更多的患者，并寻找其他snp，以了解卡培他滨与DPYD基因相关的毒性。这样就有可能调整这种药物的剂量，增加其效力并尽量减少其毒性。
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