The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment
Abstract
1. Introduction
2. Metabolic Enzymes and Genes Related to Breast Cancer Drug Metabolism
3. Pharmacogenetic Variants and Breast Cancer Drugs
3.1. Endocrine Therapy
3.1.1. Tamoxifen
3.1.2. Aromatase Inhibitors (AIs)
3.1.3. Cyclin-Dependent Kinase (CDK) 4/6 Inhibitor
3.2. Chemotherapy
3.2.1. Taxanes
3.2.2. Cyclophosphamide (CTX)
3.2.3. Anthracyclines
3.3. Anti-HER2 Targeted Therapy
3.3.1. Monoclonal Antibodies
3.3.2. Tyrosine Kinase Inhibitors (TKIs)
3.3.3. Antibody-Drug Conjugate (ADC)
4. Challenges and Future Directions
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Drug Class | Enzyme/Genetic Variant | Effect on Pharmacokinetics |
---|---|---|
Tamoxifen (SERM) | CYP2D6 | Enhanced-function allele increases symptoms and discontinuation rates; the reduced-function allele diminishes tamoxifen metabolism and efficacy. |
Aromatase Inhibitors (AIs) | CYP19A1 | Associated with baseline aromatase activity |
CYP2A6 | Reduced-function allele elevates letrozole plasma concentrations. | |
UGT1A4 and UGT2B7 | Affect drug conjugation and clearance. | |
GSTA1 *B*B | inhibited metabolism | |
CDK 4/6 Inhibitors | CYP3A4 | Higher risk of toxicity with strong CYP3A4 inhibitors |
Taxanes | CYP2C8*3 | Higher remission rates in neoadjuvant treatment, with possible increased toxicity. |
CYP3A4 | Reduced mRNA plasma level is associated with the docetaxel response rates | |
ABCB1 | Increased risk of neutropenia and diarrhea | |
SLCO1B1 521T>C | Decreased risk of mortality | |
Cyclophosphamide (CTX) | CYP2B6 516G>T and A785A>G | Poorer overall survival (OS) |
CYP2C19*2 | Related to an increased risk of adverse reactions (AEs) | |
Anthracyclines | CYP2C19*2 | Increased drug-induced AEs |
UGT2B7 161 C>T | Higher epirubicin elimination, lower risk of leukopenia | |
ABCB1 3435 C>T | Better OS but increased risk of diarrhea and neutropenia | |
SLC22A16 T>C | Increased risk of diarrhea and neutropenia | |
GSTM1 and GSTT1 deletions | Decreased recurrence and mortality rates. | |
GSTP1 313A>G | Increased risk of hematological toxicity | |
Monoclonal Antibodies | HER2 1173A>G | Increased risk of trastuzumab-induced cardiac toxicity |
FCGR2A 519A>G | Associated with reduced trastuzumab efficacy | |
FCGR3A 559T>G | Higher pCR rates with trastuzumab plus lapatinib in neoadjuvant therapy | |
ABCB1 3435 C>T | Increased resistance to chemotherapy/trastuzumab regimens | |
Tyrosine Kinase Inhibitors (TKIs) | CYP3A4 | Increased risk of lapatinib-induced hepatotoxic toxicity and associated with resistance in neratinib-resistant cells |
CYP3A5, CYP3A7 | May reduce lapatinib cytotoxicity and DNA damage | |
Antibody-drug conjugate (ADCs) | Unknown | Needs further exploration |
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Wu, X.; Xiong, H. The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment. Pharmaceutics 2024, 16, 1407. https://doi.org/10.3390/pharmaceutics16111407
Wu X, Xiong H. The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment. Pharmaceutics. 2024; 16(11):1407. https://doi.org/10.3390/pharmaceutics16111407
Chicago/Turabian StyleWu, Xinyu, and Huihua Xiong. 2024. "The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment" Pharmaceutics 16, no. 11: 1407. https://doi.org/10.3390/pharmaceutics16111407
APA StyleWu, X., & Xiong, H. (2024). The Role of Pharmacogenetic-Based Pharmacokinetic Analysis in Precise Breast Cancer Treatment. Pharmaceutics, 16(11), 1407. https://doi.org/10.3390/pharmaceutics16111407