Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity

Hahn, Roberta Zilles; Antunes, Marina Venzon; Verza, Simone Gasparín; Perassolo, Magda Susana; Suyenaga, Edna Sayuri; Schwartsmann, Gilberto; Linden, Rafael

doi:10.2174/0929867325666180622141101

Cited by 35 publications

(18 citation statements)

References 91 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…UGT1A1 is a critical phase II metabolizing enzyme involved in the metabolic inactivation of SN38, the active metabolite of irinotecan. Irinotecan is a first-line drug for the treatment of metastatic colorectal cancer (Hahn et al, 2019), so the hypomethylation status of UGT1A1 may accelerate the inactivation of irinotecan to reduce the efficacy of irinotecan. Bisulfite sequencing of UGT1A1 observed the abnormal methylation modification of specific CpG islands in UGT1A1-negative cells such as HCT-116, HCT-15, and COLO-320DM, whereas in HT-29, HT-115, and LOVO cell lines with high expression of UGT1A1, these sites were in the hypomethylation states.…”

Section: Hypomethylation Status Of Dme Genes In Cancermentioning

confidence: 99%

Epigenetic Regulation of Differentially Expressed Drug-Metabolizing Enzymes in Cancer

Wang

Jiang

et al. 2020

Drug Metab Dispos

View full text Add to dashboard Cite

Drug metabolism is a biotransformation process of drugs, catalyzed by drug-metabolizing enzymes (DMEs), including phase I DMEs and phase II DMEs. The aberrant expression of DMEs occurs in the different stages of cancer. It can contribute to the development of cancer and lead to individual variations in drug response by affecting the metabolic process of carcinogen and anticancer drugs. Apart from genetic polymorphisms, which we know the most about, current evidence indicates that epigenetic regulation is also central to the expression of DMEs. This review summarizes differentially expressed DMEs in cancer and related epigenetic changes, including DNA methylation, histone modification, and noncoding RNAs. Exploring the epigenetic regulation of differentially expressed DMEs can provide a basis for implementing individualized and rationalized medication. Meanwhile, it can promote the development of new biomarkers and targets for the diagnosis, treatment, and prognosis of cancer. SIGNIFICANCE STATEMENTThis review summarizes the aberrant expression of DMEs in cancer and the related epigenetic regulation of differentially expressed DMEs. Exploring the epigenetic regulatory mechanism of DMEs in cancer can help us to understand the role of DMEs in cancer progression and chemoresistance. Also, it provides a basis for developing new biomarkers and targets for the diagnosis, treatment, and prognosis of cancer.

show abstract

Section: Hypomethylation Status Of Dme Genes In Cancermentioning

confidence: 99%

Epigenetic Regulation of Differentially Expressed Drug-Metabolizing Enzymes in Cancer

Wang

Jiang

et al. 2020

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…Irinotecan is a topoisomerase‐1 inhibitor, a relatively classic chemotherapeutic drug. It can block topoisomerase‐1 and inhibit DNA replication and transcription 9 . The combination of irinotecan and BVZ has been proven to improve the prognosis of adult patients with high‐grade gliomas.…”

Section: What Is Known and Objectivementioning

confidence: 99%

Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta‐analysis and Systematic Review

Li²,

et al. 2020

J Clin Pharm Ther

View full text Add to dashboard Cite

What is known and objective Bevacizumab (BVZ) is an angiogenesis inhibitor that often works well with chemotherapeutic drugs for the treatment of solid intracranial tumours in children. This meta‐analysis discusses the efficacy and side effects of BVZ combined with irinotecan in the treatment of patients (younger than 21 years of age) with recurrent, progressive or refractory intracranial tumours. Methods We searched for articles published before 31 October 2018 in PubMed, EMBASE, Cochrane library and Web of Science. We selected relevant literature on the combination of BVZ and irinotecan in the treatment of children with intracranial tumours. Objective response was evaluated by combining partial response (PR), complete response (CR), stable disease (SD) and progressive disease (PD), and survival time was evaluated by combining overall survival (OS) and progression‐free survival (PFS); common side effects were also analysed. All data included were obtained from single‐arm data, with no control groups. Results and discussion A total of 13 studies involving 272 patients were included. We found that out of 41% patients who showed an objective response following the BVZ therapy combined with irinotecan, 28% achieved a PR, 13% achieved a CR, 32% showed a SD, and 43% had a PD; PFS and OS were 6.47 and 11.9 months, respectively; gastrointestinal dysfunction, leukopenia and hypertension were the three most common adverse events, accounting for 36.7%, 33.6% and 22.1%, respectively, whereas musculoskeletal disorders had the lowest occurrence, accounting for 3.9%. What is new and conclusion BVZ combined with irinotecan‐based chemotherapy had a better response and prolonged survival in the treatment of paediatric intracranial tumours than radiation therapy or chemotherapy. Gastrointestinal dysfunction, leukopenia and hypertension were the toxic side effects with the highest incidence.

show abstract

“…Delivery of Camptothecins and Synthetic Retinoid Derivatives. SN-38, the active metabolite of irinotecan, is unable to reach the market owing to its poor solubility and high toxicity (Hahn et al, 2018). Given that it is considerably more active than irinotecan, SN-38 was conjugated with tocopherol succinate to form a prodrug and was afterward encapsulated in biodegradable poly(lactide)-PEG-based NPs (Alferiev et al, 2015).…”

Section: Nontargeted Nanomedicines For Neuroblastomamentioning

confidence: 99%

Therapeutic Opportunities in Neuroblastoma Using Nanotechnology

Rodríguez-Nogales

Noguera

Couvreur

et al. 2019

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Neuroblastoma (NB) is the most common extracranial solid tumor preferentially occurring in preschoolers. Its characteristic aggressiveness and heterogeneous clinical behavior are especially visible in relapsed or refractory cases and hamper therapeutic success. Although the introduction of novel antitumor agents, such as dinutuximab, isotretinoin, irinotecan, or I-131-metaiodobenzylguanidine, has increased survival rates, the situation in high-risk NB remains dismal. Moreover, treatment is particularly aggressive in these patients, leading to short-and long-term toxicities. The extensive research performed using nanotechnology in recent decades has prompted its application as a therapeutic alternative to overcome some of the common limitations of conventional chemotherapy. Nevertheless, the therapeutic role of nanomedicine in pediatric tumors like NB is not fully elucidated, and to date, only albuminbound paclitaxel nanoparticles have reached clinic stages. In this review, we summarize the current therapeutic strategies for NB with special attention to the use of nanomedicine. We also highlight the preclinical studies on passive and active targeting nanodelivery of therapeutics in experimental NB models.

show abstract

Pharmacokinetic and Pharmacogenetic Markers of Irinotecan Toxicity

Cited by 35 publications

References 91 publications

Epigenetic Regulation of Differentially Expressed Drug-Metabolizing Enzymes in Cancer

Epigenetic Regulation of Differentially Expressed Drug-Metabolizing Enzymes in Cancer

Therapeutic effect and side effects of Bevacizumab combined with Irinotecan in the treatment of paediatric intracranial tumours: Meta‐analysis and Systematic Review

Therapeutic Opportunities in Neuroblastoma Using Nanotechnology

Contact Info

Product

Resources

About