Genomic variations associated with risk and protection against vincristine-induced peripheral neuropathy in pediatric cancer patients.

Vincristine-induced peripheral neuropathy is a common and highly debilitating toxicity from vincristine treatment that affects quality of life and often requires dose reduction, potentially affecting survival. Although previous studies demonstrated genetic factors are associated with vincristine neuropathy risk, the clinical relevance of most identified variants is limited by small sample sizes and unclear clinical phenotypes. A genome-wide association study was conducted in 1100 cases and controls matched by vincristine dose and genetic ancestry, uncovering a statistically significant (p < 5.

Machine learning model identifies genetic predictors of cisplatin-induced ototoxicity in CERS6 and TLR4.

Background: Cisplatin-induced ototoxicity remains a significant concern in pediatric cancer treatment due to its permanent impact on quality of life. Previously, genetic association analyses have been performed to detect genetic variants associated with this adverse reaction.

Methods: In this study, a combination of interpretable neural networks and Generative Adversarial Networks (GANs) was employed to identify genetic markers associated with cisplatin-induced ototoxicity.

Systematic Critical Review of Genetic Factors Associated with Cisplatin-induced Ototoxicity: Canadian Pharmacogenomics Network for Drug Safety 2022 Update.

Background: Cisplatin is commonly used to treat solid tumors; however, its use can be complicated by drug-induced hearing loss (ie, ototoxicity). The presence of certain genetic variants has been associated with the development/occurrence of cisplatin-induced ototoxicity, suggesting that genetic factors may be able to predict patients who are more likely to develop ototoxicity. The authors aimed to review genetic associations with cisplatin-induced ototoxicity and discuss their clinical relevance.

Regulates Cardiac Sensitivity to Anthracycline Chemotherapy.

Background: Anthracycline chemotherapies cause heart failure in a subset of cancer patients. We previously reported that the anthracycline doxorubicin (DOX) induces cardiotoxicity through the activation of cyclin-dependent kinase 2 (CDK2).

Objectives: The aim of this study was to determine whether retinoblastoma-like 2 (RBL2/p130), an emerging CDK2 inhibitor, regulates anthracycline sensitivity in the heart.

Intravenous N-Acetylcysteine to Prevent Cisplatin-Induced Hearing Loss in Children: A Nonrandomized Controlled Phase I Trial.

Purpose: Cisplatin-induced hearing loss (CIHL) is common and permanent. As compared with earlier otoprotectants, we hypothesized N-acetylcysteine (NAC) offers potential for stronger otoprotection through stimulation of glutathione (GSH) production. This study tested the optimal dose, safety, and efficacy of NAC to prevent CIHL.

All-trans retinoic acid (ATRA) regulates key genes in the RARG-TOP2B pathway and reduces anthracycline-induced cardiotoxicity.

The effectiveness of anthracycline chemotherapeutics (e.g., doxorubicin) is limited by anthracycline-induced cardiotoxicity (ACT).

Transcriptome-wide association study uncovers the role of essential genes in anthracycline-induced cardiotoxicity.

Anthracyclines are highly effective chemotherapeutic agents; however, their clinical utility is limited by severe anthracycline-induced cardiotoxicity (ACT). Genome-wide association studies (GWAS) have uncovered several genetic variants associated with ACT, but the impact of these findings requires further elucidation. We conducted a transcriptome-wide association study (TWAS) using our previous GWAS summary statistics (n = 280 patients) to identify gene expression-related associations with ACT.

Prevention of adverse drug effects: a pharmacogenomic approach.

Purpose Of Review: Adverse drug reactions (ADRs) are a serious burden and can negatively impact patient quality of life. One of these ADRs, anthracycline-induced cardiotoxicity (ACT), occurs in up to 65% of treated patients and can lead to congestive heart failure. Pharmacogenetic studies have helped to reveal the mechanisms of ACT and, consequently, inform current strategies to prevent ACT in the clinic.