5-fluorouracil toxicity in the treatment of colon cancer associated with the genetic polymorphism 2846 A&gt;G (rs67376798)

González-Perera, Itamar; Gutiérrez-Nicolás, Fernando; Nazco-Casariego, Gloria Julia; Ramos-Díaz, Ruth; Gil, R; Pérez-Pérez, José A; García, J González; Fuente, Guillermo A González De La

doi:10.1177/1078155216647202

Cited by 13 publications

(9 citation statements)

References 9 publications

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“…About 66 and 61% of stage II and III colon and rectal patients underwent further treatments with adjuvant chemotherapy and/or radiotherapy, respectively (12). These treatments have many side effects due to their unspecificity and cytotoxicity toward any cells that are growing and dividing (13,14). Furthermore, 54% of patients relapse even after neoadjuvant treatment (15).…”

Section: Introductionmentioning

confidence: 99%

Colorectal Cancer Immunotherapy: Options and Strategies

2020

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Colorectal cancer is the third most common cancer in the world with increasing incidence and mortality rates globally. Standard treatments for colorectal cancer have always been surgery, chemotherapy and radiotherapy which may be used in combination to treat patients. However, these treatments have many side effects due to their non-specificity and cytotoxicity toward any cells including normal cells that are growing and dividing. Furthermore, many patients succumb to relapse even after a series of treatments. Thus, it is crucial to have more alternative and effective treatments to treat CRC patients. Immunotherapy is one of the new alternatives in cancer treatment. The strategy is to utilize patients' own immune systems in combating the cancer cells. Cancer immunotherapy overcomes the issue of specificity which is the major problem in chemotherapy and radiotherapy. The normal cells with no cancer antigens are not affected. The outcomes of some cancer immunotherapy have been astonishing in some cases, but some which rely on the status of patients' own immune systems are not. Those patients who responded well to cancer immunotherapy have a better prognostic and better quality of life.

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Section: Introductionmentioning

confidence: 99%

Colorectal Cancer Immunotherapy: Options and Strategies

2020

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“…Para la segunda variante de mayor relevancia rs67376798, González-Perera et al [13], indicaron que esta variante se ha relacionado con una disminución del 30% al 70% de la actividad de DPYD. De la misma manera, observaron que los pacientes presentaron neutropenia, mucositis y diarrea.…”

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Polimorfismos genéticos asociados a toxicidad en el tratamiento con 5-fluorouracilo en pacientes con cáncer colorrectal

2022

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Introduction: Colorectal cancer is the most common malignancy of the digestive tract. The treatment is based basically on administering antitumor medications, like 5-fluorouracil (5-FU), which belongs to the antimetabolites, antineoplastic agents. However, it has been shown that there is toxicity related to genetic polymorphism in patients treated with 5-FU, including gastrointestinal symptoms, myelosuppression, and neurotoxicity. The genetic variations of four genes have been studied, including ABCB1, DPYD, MTHFR, and TYMS. Methodology: Bibliographic review based on digital articles, starting with the research of information about 5-fluorouracil as treatment of patients with colorectal cancer, its adverse reactions, polymorphisms, and toxicity. The database used is PubMed, ScienceDirect, and Scielo, published within the last ten years. It included scientific articles and studies on patients older than 18. Publications in Spanish and English as well as full-text articles. Additionally, the polymorphisms were analyzed in the NCBI (National Center for Biotechnology Information) database, from which the allelic frequencies at the global and Latin American levels were obtained. Results: A total of 11 articles were reviewed, from where we obtained data about polymorphism that developed in patients with colorectal cancer who receive treatment with 5-fluorouracil. The analyzed genes are ABCB1, DPYD, MTHFR, and TYMS. It was established that the polymorphisms trigger toxicity that manifests in different forms: diarrhea, stomatitis, mucositis, and neutropenia.

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“…Systemic chemotherapy is the primary treatment for metastatic CRC . Administration of cytotoxic chemotherapeutic agents, mainly irinotecan or oxaliplatin in combination with 5-fluorouracil and leucovorin or capecitabine (FOLFIRI/FOLFOX or CAPIRI/CAPOX regimens), is still the main strategy for CRC treatment. , However, these drugs have many side effects, due to their lack of specificity and cytotoxicity toward normal cells. , Although some FDA-approved targeted drugs, such as the anti-VEGF family inhibitors fruquintinib and regorafenib, the anti-EGFR antibody (Ab) cetuximab, and the anti-VEGFR Ab bevacizumab, are used in clinical applications, the efficacy of VEGFR/EGFR-targeting drugs is poor, and its adverse effects, especially drug resistance, are difficult to manage. , In addition, exploiting the immune system is a novel and promising approach in cancer treatment. , However, therapies employing only immune checkpoint inhibitors, represented by the anti-PD-1 Ab, have primarily benefited a small portion of MSI-H (high microsatellite instability) CRC patients and do not elicit responses in 90% CRC patients who were associated with microsatellite stability (MSS) . MSS-CRC represents the low T cell-inflamed gene signature along with the low tumor mutational burden (TMB) as the markers for placing MSS-CRC in the category of “cold” immunity. , Although the anti-PD-1 Ab can upregulate the cytotoxic effect of cytotoxic T lymphocytes (CTLs) by releasing the exhaustion, the unsatisfactory therapeutic effect of the anti-PD-1 Ab for MSS-CRC may be due to the “cold” tumor immune microenvironment (TIME) of lacking CTLs .…”

Section: Introductionmentioning

confidence: 99%

Discovery of Novel 3-Phenylpiperidine Derivatives Targeting the β-Catenin/B-Cell Lymphoma 9 Interaction as a Single Agent and in Combination with the Anti-PD-1 Antibody for the Treatment of Colorectal Cancer

et al. 2023

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Direct disruption of the β-catenin/B-cell lymphoma 9 (BCL9) protein−protein interaction (PPI) is a potential strategy for colorectal cancer (CRC) treatment through inhibiting oncogenic Wnt activity. Herein, a series of 3-phenylpiperidine derivatives were synthesized and evaluated as β-catenin/BCL9 PPI inhibitors. Among them, compound 41 showed the best IC 50 (0.72 μM) in a competitive fluorescence polarization assay and a K D value of 0.26 μM for the β-catenin protein. This compound selectively inhibited the growth of CRC cells, suppressed Wnt signaling transactivation, and downregulated oncogenic Wnt target gene expression. In vivo, 41 showed potent anti-CRC activity and promoted the infiltration and function of cytotoxic T lymphocytes while decreasing the infiltration of regulatory T-cells (Tregs). Furthermore, the combination of 41 and the anti-PD-1 antibody (Ab) efficiently enhanced anti-CRC efficacy, first verifying the in vivo efficacy of the small-molecule β-catenin/BCL9 PPI inhibitor and anti-PD-1 Ab in combination.

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5-fluorouracil toxicity in the treatment of colon cancer associated with the genetic polymorphism 2846 A>G (rs67376798)

Cited by 13 publications

References 9 publications

Colorectal Cancer Immunotherapy: Options and Strategies

Colorectal Cancer Immunotherapy: Options and Strategies

Polimorfismos genéticos asociados a toxicidad en el tratamiento con 5-fluorouracilo en pacientes con cáncer colorrectal

Discovery of Novel 3-Phenylpiperidine Derivatives Targeting the β-Catenin/B-Cell Lymphoma 9 Interaction as a Single Agent and in Combination with the Anti-PD-1 Antibody for the Treatment of Colorectal Cancer

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