مقالات پذیرفته شده در نهمین کنگره بین المللی زیست پزشکی
Pharmacogenetic Approaches to Ovarian Cancer Management
Pharmacogenetic Approaches to Ovarian Cancer Management
Reza Kalantari,1,*Mohammad Azadbakht,2Nila Navaei,3
1. Research Institute for Herbal Medicines and Metabolic Disorders, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 2. Professor, Department of Pharmacognosy and Biotechnology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. 3. Pharm.D Candidate Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
Introduction: Due to its asymptomatic early stages and the lack of population-based screening programs, ovarian cancer is one of the most deadly gynecologic cancers globally. Cytoreductive surgery and platinum-taxane chemotherapy have improved, but treatment response and toxicity vary, requiring precision techniques integrating molecular, pharmacogenetic, and pharmacological knowledge. CYP3A enzymes, ABC efflux and uptake transporters, and drug-binding proteins modulate the pharmacokinetics of taxanes, particularly docetaxel, affecting systemic exposure, efficacy, and toxicity. Pharmacogenetic variations in these pathways can influence pharmacodynamic and pharmacokinetic outcomes, allowing customized dosing to maximize effectiveness and minimize side effects. Targeted biologics like bevacizumab and zoledronic acid complicate pharmacology. Translational pharmacology must link molecular indicators to clinical outcomes since patient-specific genetic architecture might affect treatment response and side effects. This review summarizes 2015–2025 literature on ovarian cancer pharmacogenetic determinants and pharmacological therapies, focusing on molecular risk assessment, diagnostic biomarkers, and therapeutic optimization. These ideas can be used for individual patient care in a scenario including prolonged docetaxel therapy, zoledronic acid maintenance, and full pharmacogenetic screening.
Methods: A comprehensive PubMed, Scopus, and Web of Science search was conducted for 2015–2025 studies. Ovarian cancer, pharmacogenetics, docetaxel, zoledronic acid, targeted therapy, drug metabolism, toxicity, and therapeutic outcomes were keywords. Included were clinical trials, observational studies, translational research, and high-quality case series on pharmacogenetic factors, pharmacokinetics, pharmacodynamics, and therapeutic efficacy or toxicity. Studies without ovarian cancer emphasis, pharmacogenetic or pharmacologic data, or methodological rigor were rejected. Data extraction included research design, patient demographics, treatment regimens, genetic variants, pharmacokinetic and pharmacodynamic results, and clinical outcomes. Qualitative synthesis highlighted mechanistic discoveries, genotype–phenotype relationships, and risk-stratification biomarkers. Drug response and adverse-event susceptibility varied among individuals across studies. A sample patient with prolonged docetaxel therapy, zoledronic acid maintenance, and complete pharmacogenetic evaluation showed molecular data translation into clinical decision-making.
Results: Synthesis of literature: Pharmacogenetic variability significantly impacts cytotoxic and targeted ovarian cancer treatments' pharmacokinetics and pharmacodynamics. Docetaxel is metabolized by CYP3A4/5 and transported via ABCB1 and ABCC2. Polymorphisms affect systemic exposure, effectiveness, and toxicity, including myelosuppression, neuropathy, and mucositis. Genotype-guided dosage lowers side effects and improves treatment success. Molecular profiles show patient-specific response variability for VEGF-targeted biologics like bevacizumab. Zoledronic acid and other adjuvant bone-modifying treatments protect skeletal structures during chemotherapy, but pharmacodynamic effects vary. Integrating pharmacogenetic and biomarker data enhances therapeutic outcome and toxicity prediction. An example: A 52-year-old lady (56 kg) with hypothyroidism and mild metabolic abnormalities (elevated cholesterol, borderline fasting glucose) displayed bilateral complex adnexal masses (left: 105 × 70 mm; right: 56 × 33 mm) on transvaginal ultrasound and confirmed by MRI. Omental hypertrophy and mild ascites were found. Preoperative CA125 and ROMA index were high, but CBC, liver, and renal function were normal. Father had hematologic cancer. After cytoreductive surgery, pharmacogenetic-guided systemic therapy began. Six cycles of intravenous docetaxel (20/80 mg) with dexamethasone premedication, antiemetics, and saline infusion were given every three weeks. For 22 cycles, 400 mg of bevacizumab was given every three weeks, and zoledronic acid was given biannually to reduce skeletal effects. No harmful mutations were found in MPLA analysis for BRCA1&2 and an NGS hereditary cancer panel, allowing full-dose administration without toxicity interruptions. Hematologic, hepatic, and renal indices stabilized. Regular tumor markers confirmed disease control after treatment, supportive therapy, and bone-density monitoring treated alopecia, arthralgia, and osteoporosis.
Conclusion: Pharmacogenetic-guided ovarian cancer treatment is shown in this example. CYP3A4/5 metabolism and ABC transporter activity affect docetaxel pharmacokinetics, affecting systemic exposure and toxicity. Pharmacogenetic assessment allowed safe and effective standard dosing. Zoledronic acid protected the skeletal structure, while bevacizumab caused patient-specific molecular responses. Adjunctive medicines are crucial to comprehensive management. Carboplatin, paclitaxel, and PARP inhibitors (olaparib, niraparib) also show genotype-dependent variability related to DNA repair and transporter polymorphisms. Precision oncology optimises therapeutic efficacy and minimises side effects by integrating molecular biomarkers, pharmacogenetic profiling, and therapy monitoring. Stable CBC, hepatic, and renal parameters showed tolerance, while CA125 and ROMA index normalization showed efficacy. Personalized ovarian cancer care includes pharmacogenetic-guided dosing, targeted biologics, and supportive therapy. In modern ovarian cancer management, personalized medication improves disease control, toxicity, and patient outcomes.