ANTI-CANCER DRUGS-5

 Oncology & Pharmacology ﻢﻴﺣﺮﻟا ﻦﻤﺣﺮﻟا ﻪﻠﻟا ﻢﺴﺑﻢﻴﺣﺮﻟا ﻦﻤﺣﺮﻟا ﻪﻠﻟا ﻢﺴﺑ Bismillah Rehman Raheem Bismillah Rehman Raheem In the Name of Allah, the Most Gracious, the Most Merciful .

Supervisor  Dr GR Bhurgri MBBS, MPhil, PhD, FCPS  Supervisor  Department of Pharmacology  Oncology & Cancer Research  2026 - Hormonal Drugs for Cancer Treatment.

Learning Objectives  Understand the concept of hormonal therapy in cancer treatment  Describe the pharmacodynamics of hormonal cancer drugs  Explain the pharmacokinetics of hormonal cancer drugs  Identify therapeutic uses of hormonal therapy  Recognize adverse effects of hormonal therapy  List contraindications of hormonal therapy  2026 - Hormonal Drugs for Cancer Treatment.

Introduction to Hormonal Drugs for Cancer Treatment  Definition Hormone therapy slows or stops cancer growth that uses hormones to grow  Hormone-Sensitive Cancers Breast • Prostate • Endometrial • Ovarian  Main Approaches Blocking hormone production Interfering with hormone behavior  Administration Routes Oral Injection Surgery Hormonal Therapy Targeted Cancer Treatment  2026 - Hormonal Drugs for Cancer Treatment.

Pharmacodynamics of Hormonal Cancer Drugs  Receptor Antagonism/Blockade Tamoxifen: Blocks estrogen receptor interactions Anti-androgens: Block testosterone receptor interactions  Hormone Depletion GnRH agonists/antagonists: Suppress ovarian estrogen LHRH analogs: Reduce testosterone production Aromatase inhibitors: Prevent androgen-to-estrogen conversion  Selective Receptor Modulators/Degraders SERMs: Selective Estrogen Receptor Modulators SERDs: Selective Estrogen Receptor Degraders SARMs: Selective Androgen Receptor Modulators  Enzyme Inhibitors Aromatase inhibitors: Anastrozole, Letrozole, Exemestane CYP17A1 inhibitors: Abiraterone  2026 - Hormonal Drugs for Cancer Treatment.

Pharmacokinetics of Hormonal Cancer Drugs  Absorption Oral bioavailability varies by drug Tamoxifen: Affected by dietary status IM and subcutaneous injections available  Distribution Widely distributed throughout the body Cross cell membranes to reach target receptors High protein binding for many agents  Metabolism Extensive hepatic metabolism (CYP450 enzymes) Tamoxifen: Metabolized to active metabolites (endoxifen) Genetic factors affect metabolism (pharmacogenetics)  Excretion Primarily renal and fecal excretion Half-lives: Tamoxifen 5-7 days AIs 2-5 days LHRH 2-4 hrs  2026 - Hormonal Drugs for Cancer Treatment.

Therapeutic Uses  Breast Cancer Adjuvant therapy (5-10 years) Neoadjuvant therapy Metastatic breast cancer Prevention in high-risk  Prostate Cancer Androgen deprivation therapy (ADT) Metastatic castration-sensitive Metastatic castration-resistant Combined with radiation/chemo  Other Cancers Endometrial: Advanced/recurrent Ovarian: Hormone- sensitive Kidney: Selected cases  Treatment Duration  Early-Stage Disease 5-10 Years  Metastatic Disease Continued until progression  2026 - Hormonal Drugs for Cancer Treatment.

Adverse Effects  Women Breast Cancer Hot flashes Vaginal dryness Menopausal symptoms Bone thinning Joint/muscle pain Mood changes Depression Blood clots Weight gain Fatigue Hair thinning  Men Prostate Cancer Hot flashes Loss of libido Erectile dysfunction Breast swelling/tenderness Bone thinning Fractures Muscle loss Weight gain Fatigue Memory problems Depression Loss of body hair  2026 - Hormonal Drugs for Cancer Treatment.

Contraindications  Aromatase Inhibitors Hypersensitivity: Anaphylaxis, angioedema, urticaria Pregnancy: Fetal harm, pregnancy loss Premenopausal women: No clinical benefit  Tamoxifen Pregnancy: Teratogenic effects History of blood clots: DVT, pulmonary embolism History of stroke Severe liver disease  General Contraindications Hormone receptor-negative cancers Known hypersensitivity to hormonal agents Uncontrolled cardiovascular disease Severe renal or hepatic impairment  Drug Interactions Tamoxifen + CYP2D6 inhibitors: Reduces efficacy Hormonal therapy + warfarin: Increased bleeding risk Estrogen-containing products: Interfere with therapy  2026 - Hormonal Drugs for Cancer Treatment.

ميحرلا نمحرلا هللا مسب Bismillah Rehman Raheem In the name of Allah, the Most Gracious, the Most Merciful.

SUPERVISOR  Academic Supervisor Supervisor Name Dr GR Bhurgri Academic Qualifications MBBS MPhil PhD FCPS.

LEARNING OBJECTIVES  Introduction Targeted chemotherapy drugs in cancer treatment  Pharmacodynamics Mechanisms of action and drug-receptor interactions  Pharmacokinetics ADME processes in the body  Therapeutic Uses Cancer types and drug indications  Adverse Effects Common and serious side effects  Contraindications Precautions and drug restrictions.

INTRODUCTION TO TARGETED CHEMOTHERAPY  What is Targeted Therapy? Precision medicine that attacks specific cancer cell targets with minimal damage to normal cells  vs Conventional Chemotherapy Targeted therapy selectively inhibits molecular pathways, unlike traditional chemotherapy's broad cytotoxic approach  Clinical Impact Improved therapeutic index, enhanced treatment response, reduced systemic toxicity in modern oncology.

PHARMACODYNAMICS  Target Identification Specific molecular targets: growth factor receptors, tyrosine kinases, angiogenesis pathways  Drug-Receptor Interaction High-affinity binding to specific receptors, blocking ligand-receptor complexes and downstream signaling  Signal Pathway Inhibition Disruption of critical cancer pathways: PI3K/AKT, MAPK/ERK, JAK/STAT, and apoptotic regulation  Cellular Effects Inhibition of proliferation, induction of apoptosis, anti-angiogenesis, and metastasis prevention.

PHARMACOKINETICS  Absorption Intravenous administration preferred; bioavailability varies with formulation  Distribution High tissue penetration; blood- brain barrier crossing varies by molecular weight  Metabolism Hepatic CYP450 enzymes; drug interactions significant; metabolic pathways vary  Excretion Renal elimination predominant; hepatic excretion for some agents; half-life considerations  Therapeutic drug monitoring essential for dose optimization and toxicity management.

THERAPEUTIC USES  Monoclonal Antibodies Trastuzumab (HER2+ breast cancer), Rituximab (CD20+ lymphomas), Bevacizumab (anti-angiogenesis)  Tyrosine Kinase Inhibitors Imatinib (CML, GIST), Erlotinib/Gefitinib (EGFR+ NSCLC), Sunitinib (RCC, GIST)  PARP Inhibitors Olaparib, Niraparib (BRCA-mutated ovarian, breast, pancreatic cancers)  Immunomodulators & Checkpoint Inhibitors Nivolumab, Pembrolizumab (PD-1/PD-L1 inhibitors) - multiple solid tumors.

ADVERSE EFFECTS  Common Adverse Effects Fatigue, rash, diarrhea, nausea, hypertension, hepatotoxicity, proteinuria dermatology Skin & Mucosal Toxicities Hand-foot syndrome, mucositis, dry skin, pruritus, acneiform eruptions  Cardiovascular Effects Cardiotoxicity, QT prolongation, hypertension, thromboembolism  Hematologic & Immunologic Neutropenia, anemia, thrombocytopenia, infusion reactions  Serious/Grade 3-4 Toxicities Pneumonitis, hemorrhage, perforation, severe infections, endocrine dysfunction.

CONTRAINDICATIONS  Absolute Contraindications Known hypersensitivity, severe uncontrolled infections, pregnancy, lactation, severe organ dysfunction  Relative Contraindications Poor performance status, uncontrolled comorbidities, recent major surgery, active bleeding disorders  Significant Drug Interactions CYP450 inhibitors/inducers, other antineoplastic agents, immunosuppressants, QT-prolonging drugs  Special Population Precautions Elderly patients, pediatric patients, renal/hepatic impairment, genetic polymorphisms affecting drug metabolism  Mandatory Monitoring Baseline cardiac function, liver/kidney function tests, blood counts, pregnancy testing, regular clinical assessments.

 Hormonal Therapy  Targeted Therapy  Viva & MCQs Pharmacology of Hormonal Drugs and Targeted Therapy in Cancer Treatment  Review Questions.

Overview of Cancer Pharmacology  Hormonal Drugs Glucocorticoids Prednisone, Dexamethasone Antiestrogens Tamoxifen, Fulvestrant Anti-androgens Flutamide, Nilutamide, Bicalutamide GnRH Analogues Leuprolide, Goserelin, Degarelix  Targeted Therapy Drugs mTOR Inhibitors Temsirolimus, Everolimus HER2 Inhibitors Trastuzumab, Pertuzumab PD-1 Inhibitors Pembrolizumab, Nivolumab VEGF Inhibitors Axitinib, Bevacizumab PARP Inhibitors Olaparib, Rucaparib.

 Viva Questions 1 Tamoxifen Mechanism Explain the mechanism of action of tamoxifen in the treatment of breast cancer. Answer: • Competitive ER antagonist • Inhibits estrogen binding • Blocks ER dimerization • Downregulates gene expression 2 mTOR Inhibitors Discuss the molecular targets of mTOR inhibitors in cancer therapy and provide an example. Answer: • Inhibits PI3K/Akt/mTOR pathway • Blocks cell proliferation • Reduces angiogenesis • Example: Temsirolimus 3 PARP Inhibitors Describe the mechanism of action of PARP inhibitors in cancer treatment and their clinical application. Answer: • Blocks DNA repair (PARP enzyme) • Synthetically lethal in BRCA-mutated cells • Induces apoptosis • Used in ovarian, breast cancer Prepare concise, well-structured responses focusing on pharmacological mechanisms and clinical applications..

 Multiple Choice Questions 1. Tamoxifen is classified as which type of drug? A) Aromatase inhibitor B) SERM ✓ Correct C) GnRH agonist D) Anti-androgen E) mTOR inhibitor 2. Which drug targets the PI3K/Akt/mTOR pathway? A) Trastuzumab B) Pembrolizumab C) Temsirolimus ✓ Correct D) Olaparib E) Axitinib 3. Rucaparib inhibits which enzyme? A) BCR-ABL B) mTOR C) PARP ✓ Correct D) Topoisomerase E) HER2 4. Which is an anti-androgen used in prostate cancer? A) Leuprolide B) Flutamide ✓ Correct C) Tamoxifen D) Bevacizumab E) Nivolumab 5. Trastuzumab targets which receptor in breast cancer? A) HER2/neu ✓ Correct B) EGFR C) PD-1 D) VEGF E) PARP Select the single best answer for each question. Correct answers are marked..