UGT1A1*1*1

These analyses support the approved SG dosing regimen of 10 mg/kg as intravenous infusion on days 1 and 8 of 21-day cycles and did not identify a need for dose adjustment based on evaluated covariates or disease characteristics.

The UGT1A1 level may be a biomarker for early diagnosis of cancer. Meanwhile, UGT1A1 plays a crucial role in pancreatic cancer, and the combination of chrysin and cisplatin may provide effective ideas for pancreatic cancer treatment.

P2, N=182, Active, not recruiting, NuCana plc | Recruiting --> Active, not recruiting

Real-world TIC incidence is higher compared to randomized clinical trials and biomarkers with potential predictive value aren't available. Our preliminary data, as proof of concept, could suggest a predictive role of pharmacogenomic approach in the identification of cardiotoxicity risk biomarkers for anti-HER2 treatment.

One hundred and seven patients received irinotecan treatment and three patients with AA type received paclitaxel treatment. Individual irinotecan treatment shows encouraging survival and tolerability outcomes in patients with GG/GA subtype. Irinotecan may be not suitable for patients with AA subtype.

Silencing of Pxr further confirmed that OA-mediated upregulation of proliferation-related proteins depended on PXR. The current study illustrated that OA exhibited a significant promoting effect on liver regeneration following PHx, potentially through regulation of the PXR signaling pathway to accelerate liver recovery.

This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

The precise description of the allelic distribution of the variants of interest in our reference populations is information of great interest for the management of the prescription of these antineoplastic drugs. We characterized the allelic distribution of the UGT1A1*28 variant (rs3064744), as well as the DPYD*2A (rs3918290) variant, c.1679T>G (rs55886062), c.2846A>T (rs67376798) and c.1129-5923C>G (rs75017182; HapB3) in series of 5251 patients who are going to receive treatment with irinotecan and fluoropyrimidines, representative of Valencian, Aragonese and Western Andalusian populations.

These hepatic impairment effects reduced between-subject variability by only 5%-8% for their respective parameter, with a large amount of remaining unexplained variability. With further validation, this model can be leveraged to assess the need for dose adjustments in this patient population.

P1, N=40, Completed, Celgene | Active, not recruiting --> Completed

P2, N=171, Recruiting, NuCana plc | Trial completion date: Dec 2024 --> Mar 2025 | Trial primary completion date: Jun 2024 --> Sep 2024

P3; Trial completion date: Dec 2023 --> Mar 2024

Lastly, we assessed their expression in different tissues, including normal bladder and BC samples. The drug-metabolizing pathway plays a relevant role in BC, and our review discusses a list of genes that could provide clues for further exploration of susceptibility and prognostic biomarkers.

Germline DNA genetic variants may contribute to the prediction of irinotecan-induced grade 4 neutropenia when incorporated into a population pharmacokinetic/pharmacodynamic model. This approach is generalizable to drugs that induce neutropenia and ultimately allows for personalized intervention to enhance patient safety.

P1/2, N=345, Completed, Celgene | Active, not recruiting --> Completed

The knowledge regarding UGT1A1 polymorphism and its clinical relevance will be reviewed in this article, as well as the published literature on the association between UGT1A1 polymorphism and the toxicity risk of irinotecan as well as sacituzumab govitecan. The current recommendations and guidelines on UGT1A1 testing will be discussed in detail in the hopes of providing guidance to oncologists in their clinical practice.

P1, N=78, Recruiting, Shanghai Zhongshan Hospital

Our results revealed a distinct miR profile associated with dysregulated genes. The miRs and genes identified in this study may be used in the future as biomarkers and serve as potential therapeutic targets in EAC.

With longer follow-up, the ORR remains high in patients with heavily pretreated LA or mUC. Safety data were consistent with the known SG toxicity profile. AE incidence varied across UGT1A1 subgroups; however, discontinuation rates remained relatively low for all groups.

APRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits.

P2, N=1, Terminated, Hackensack Meridian Health | N=43 --> 1 | Trial completion date: May 2026 --> Nov 2023 | Recruiting --> Terminated | Trial primary completion date: May 2025 --> Nov 2023; Low Accrual

All patients received preoperative radiotherapy (50 Gy/25 fractions) with concurrent irinotecan (UGT1A1*1*1: 80 mg/m ; UGT1A1*1*28: 65 mg/m ) and capecitabine (CapIri). We also validated the correlation between UGT1A1*6 polymorphism and SN-38 concentration, along with the clinical efficacy of irinotecan. In conclusion, our study identified the relatively optimal timepoint and concentration range for monitoring SN38 concentrations and revealed the clinical significance of UGT1A1*6 and UGT1A1*28 polymorphisms in guiding irinotecan administration, offering meaningful insights for personalised irinotecan dosing.

P2; N=6; Active, not recruiting; Sponsor:University of Florida

P2, N=45, Active, not recruiting, University of Florida

This regimen leads to acceptable clinical outcomes with manageable AEs. However, the effects on survival and safety outcomes could only be speculated, and further studies are needed because of the sample size, the follow-up for the OS evaluation, and the non-uniformity in all the variables considered in the two groups.

Combining an optimized variant-calling pipeline and with direct phasing analysis, LRS is a robust technique for PGx analysis that can minimize the risk of mis-haplotyping.

P2, N=176, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Dec 2025 | Trial primary completion date: Dec 2023 --> Dec 2025

P2, N=78, Recruiting, Canadian Cancer Trials Group

P=N/A, N=5000, Not yet recruiting, Hunter Medical Research Unit

P1, N=24, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: Jul 2024 --> Dec 2023

Combination treatment of regorafenib plus FOLFIRI with dose-escalated irinotecan according to UGT1A1genotyping results in a significant better PFS and comparable AEs. Moreover, patients with RAS wild type of CRC would be more beneficial for this combination treatment.

229 females and 238 males (median age at diagnosis 47 yrs (range 11-90) had 955 separate TKI episodes: imatinib 406, dasatinib 222, nilotinib 189, bosutinib 87, ponatinib 28 and asciminib 23. With the exception of asciminib the previous association of TKI, homozygous Gilbert and hyperbilirubinemia was confirmed. Grade 1 transaminitis is common on all TKIs, with higher grades of severity most frequent on bosutinib. Patients experiencing abnormal transaminases on 1 st line TKI are likely to have similar problems on 2 nd and 3 rd line agents, with a trend to higher incidence/severity on nilotinib compared to dasatinib.

Other tested covariates, including body weight, creatinine clearance, aspartate transaminase, alanine transaminase, bilirubin, albumin, alpha 1-acid glycoprotein, race, UGT1A1 genotype, recent ruxolitinib treatment in MF, and CYP3A4 inducer/inhibitor concomitant medications, were not significant. Tumor type influenced navtemadlin exposure with simulated exposure in R/R MF patients at the selected Phase 3 dose of 240 mg comparable to exposures in MCC patients at 180 mg, the selected Phase 2 dose for that indication. Cancer-associated inflammation and/or treatment history, as well as age and female sex, may increase navtemadlin exposure. The PD marker MIC-1 responds to navtemadlin in a concentration-dependent fashion.

According to EORTC criteria, two patients (10%) had a probable IFI on day 14, and antifungal therapy with liposomal amphotericin B was started [3]...Isavuconazonium or posaconazole for antifungal prophylaxis in patients with acute myeloid leukemia... Twenty patients were included: 9 were women (45%) with a median age of 67 years old (±10. 5) and a median Charlson Comorbidity Index of 5 (±1. 3).

P1; Phase classification: P1b --> P1

We showed that the accumulation of UGT1A1 variants or the rarity of the variation is associated with a better prognosis, and the effect magnitude correlates with UGT1A1 deficiency. This study demonstrates the therapeutic potential of host UGT1A1 variations underlying GS against HBV infection outcomes.

PGx-guided treatment strategy may represent a cost-saving option compared to the existing conventional therapeutic approach for colorectal cancer patient management in the National Health Service of Italy.

Based on these in vitro findings, soticlestat has well-characterized metabolism and limited victim and perpetrator DDI potential leading to minimal concern of clinical DDI risk.

Our results demonstrate that 7-O-glucuronidation is the major metabolic pathway of PEC in human tissues, while UGT1A1, 1A3 and 1A9 are key contributing enzymes responsible for PEC-7-O-glucuronidation in human liver. It is also found that PEC 7-O-glucuronidation significantly weakens the Nrf2 and PPAR agonist effects. All these findings are very helpful for the pharmacologists to deep understand the metabolic rates of PEC in humans.

P2; Recruiting --> Active, not recruiting | N=78 --> 6

P1, N=80, Recruiting, OHSU Knight Cancer Institute | Trial completion date: Feb 2026 --> Feb 2028 | Trial primary completion date: Jun 2024 --> Jun 2026

P3, N=504, Recruiting, Acrotech Biopharma Inc. | Not yet recruiting --> Recruiting