Clinical Biochemistry: Prostate Cancer — Pathophysiology, Biomarkers and Therapeutic Targets

Biochemistry · Basic Sciences

How it begins

La próstata es una glándula tubuloalveolar exocrina perteneciente al sistema reproductor masculino, cuyo peso en un adulto joven oscila entre los 11 y 20 gramos. Histológicamente, se compone de un compartimento epitelial y un estroma fibromuscular altamente organizado. Desde una perspectiva anatómica y funcional, según el esquema de McNeal , la próstata se subdivide en cuatro zonas bien delimitadas, cuya relevancia…

What it covers

1. Histobiology and Cellular Organization of the Prostate Gland
2. Biogenesis, Biochemistry and Regulation of PSA
3. · PSA Proteolytic Processing Cascade
4. · Mechanism of Enzymatic Action of PSA
5. Plasma Dynamics and Molecular Forms of PSA
6. · Distribution of PSA Fractions in Blood
7. · Dynamic and Kinetic Parameters of PSA Elevation
8. Advanced Second Generation Serum Biomarkers
9. · The [-2]proPSA Isoform and its Biological Relevance
10. · Prostate Health Index - Prostate Health Index (phi)
11. · The Panel of the Four Calicreines: 4Kscore
12. Urinary Biomarkers and Liquid Biopsy
13. · PCA3 (Prostate Cancer Gene 3)
14. · TMPRSS2-ERG Gene Fusion
15. · Exosomal Detection: The ExoDx Prostate (EPI) Assay
16. Molecular Physiopathology of the Androgen Receptor (AR)
17. · Dynamics of Cytoplasmic Activation and Chaperonization
18. The Hypothalamic-Pituitary-Testicular-Adrenal Axis and Androgen Synthesis
19. · Regulation of the Hypothalamus-Pituitary-Testicle Axis
20. · The Testicular Steroidogenesis Pathway
21. · The Adrenal Androgenic Contribution
22. · Intracellular Metabolism in the Prostate Tissue: 5α-Reductase
23. Molecular Pathophysiology of Castration Resistant Prostate Cancer (CRPC)
24. · 1. AR Amplification and Overexpression
25. · 2. Gain-of-Function Mutations in the LBD Domain
26. · 3. The AR-V7 Splicing Variant (Constitutively Active)
27. · 4. De Novo Intratumoral Steroidogenesis
28. · 5. Cross Activation through Kinase Pathways (Crosstalk)
29. Altered Oncogenic Signaling Pathways in Prostate Cancer
30. · The PI3K/Akt/mTOR Pathway and the Loss of the Tumor Suppressor PTEN
31. · Defects in DNA Damage Repair Mechanisms (DDR)
32. Precision Histopathological and Immunohistochemical Classification
33. · The Gleason System and the ISUP Grade Groups
34. · Differential diagnostic immunohistochemistry: The PIN4 Cocktail
35. · Neuroendocrine Differentiation Markers
36. Reprogramming and Biochemistry of Intermediate Metabolism
37. · Energy Metabolism in the Normal Luminal Epithelial Cell
38. · The Oncogenic Metabolic Switch (Neoplastic Reprogramming)
39. · The De Novo Lipogenesis Pathway
40. Genomics, Epigenomics and Hereditary Alterations
41. · Germinal Genetic Susceptibility: High Risk Heritability
42. · Epigenetic Mechanisms of Neoplastic Transformation
43. Diagnosis, Staging and Clinical Prediction Models
44. · Digital Rectal Examination (DRE - Digital Rectal Examination)
45. · Multiparametric Magnetic Resonance (mpMRI) and PI-RADS System v2.1
46. · Magnetic Resonance Fusion Biopsy and Ultrasound
47. · PSMA Positron Emission Tomography: PET-CT with ⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL
48. First Line Hormonal Therapeutics and Androgen Deprivation (ADT)
49. · 1. LHRH (GnRH) Agonists: Desensitization and the Flare Phenomenon
50. · 2. LHRH (GnRH) Antagonists: Immediate Direct Blockade
51. · 3. First Generation Nonsteroidal Antiandrogens
52. New Generation Hormonal Therapies (ARAT/ART)
53. · 1. Second Generation Antagonists: Enzalutamide, Apalutamide and Darolutamide
54. · 2. Abiraterone Acetate: Multiorgan Steroidogenesis Inhibitor
55. Chemotherapy, Immunotherapy and Precision Targeted Therapies
56. · 1. Cytotoxic Chemotherapy: Taxanes
57. · 2. PARP Inhibitors in Synthetic Lethality: Olaparib and Rucaparib
58. · 3. Autologous Active Cellular Immunotherapy: Sipuleucel-T
59. Molecular Theranostics and Nuclear Precision Medicine
60. · Pluvicto Action Mechanism (¹⁷⁷Lu-PSMA-617)
61. · Directed Therapy with Alpha Emitters: Actinium-225 (²²⁵Ac-PSMA-617)
62. Summary of Clinical Correlations and Integration of Therapeutic Algorithms
63. · Precision Pharmacology and Molecular Targets in Prostate Cancer