From Molecular Biology to Precision Oncology
Learning Objectives
By the end of this session participants will:
Understand the molecular basis of cancer
Identify key cancer-driving molecules
Recognize the role of biomarkers in diagnosis
Explore targeted therapies and immunotherapy
Appreciate the future of precision oncology
The Global Cancer Burden
Why Molecular Oncology Matters
Cancer remains one of the leading causes of death worldwide
Millions of new diagnoses each year
Significant healthcare burden
Need for earlier detection and personalized treatment
Key Message
Understanding molecular mechanisms is essential for improving outcomes.
Cancer as a Molecular Disease
Definition
Cancer develops when genetic and molecular alterations disrupt normal cellular controls.
Normal Cell → Genetic Alteration → Cellular Dysregulation → Tumor Formation → Metastasis
Hallmarks
Sustained proliferation
Resistance to cell death
Angiogenesis
Immune evasion
Metastatic potential
Normal Cell Cycle Regulation
Cell Cycle Phases
G1 Phase
S Phase
G2 Phase
Mitosis
Regulatory Components
Cyclins
Cyclin-dependent kinases (CDKs)
Tumor suppressor proteins
Clinical Relevance
Disruption of these controls contributes to cancer development.
Molecular Mechanisms of Carcinogenesis
Causes of Molecular Damage
Tobacco exposure
Radiation
Environmental carcinogens
Viral infections
Chronic inflammation
Hereditary mutations
Result
Accumulation of molecular abnormalities over time.
DNA Mutations in Cancer
Types
Point mutations
Insertions
Deletions
Copy number variations
Chromosomal translocations
Consequences
Activation of oncogenes
Loss of tumor suppressors
Genomic instability
Oncogenes
Definition
Mutated genes that promote uncontrolled growth.
Important Examples
KRAS
NRAS
MYC
HER2
BRAF
ALK
Clinical Significance
Targetable molecular drivers in many cancers.
Tumor Suppressor Genes
Function
Prevent uncontrolled proliferation.
Key Examples
TP53
RB1
BRCA1
BRCA2
PTEN
Impact
Loss of function increases cancer risk.
The p53 Pathway
"Guardian of the Genome"
Functions:
DNA repair
Cell cycle arrest
Apoptosis induction
Clinical Significance
TP53 alterations occur in over half of human cancers.
Epigenetics in Cancer
Epigenetic Changes
DNA methylation
Histone modification
Chromatin remodeling
Effects
Gene silencing
Oncogene activation
Therapy resistance
Importance
Potential biomarkers and therapeutic targets.
RNA Molecules in Cancer
Types
mRNA
microRNA (miRNA)
siRNA
lncRNA
Circular RNA
Functions
Regulation of gene expression
Tumor progression
Metastasis
Protein Biomarkers
Cancer-Associated Proteins
EGFR
HER2
VEGF
PD-L1
c-MET
Clinical Utility
Diagnosis
Prognosis
Therapy selection
Cancer Signaling Pathways
Major Pathways
MAPK
PI3K/AKT/mTOR
Wnt/β-Catenin
JAK/STAT
Notch
Outcomes
Cell survival
Growth
Migrationv
Resistance
Angiogenesis Molecules -
What is Angiogenesis?
Formation of new blood vessels.
Key Molecules
VEGF
VEGFR
PDGF
FGF
Therapeutic Targets
Anti-angiogenic therapies.
Tumor Microenvironment
Components
Cancer cells
Immune cells
Fibroblasts
Endothelial cells
Extracellular matrix
Importance
Influences treatment response and progression.
Immune Checkpoint Molecules
Major Checkpoints
PD-1
PD-L1
CTLA-4
Function
Cancer cells suppress immune attack.
Clinical Impact
Foundation of modern immunotherapy.
Molecular Biomarkers
Diagnostic Biomarkers
PSA
CA-125
CEA
AFP
Predictive Biomarkers
HER2
EGFR
PD-L1
MSI-H
Liquid Biopsy and ctDNA
What is ctDNA?
Circulating tumor DNA released into blood.
Advantages
Minimally invasive
Real-time monitoring
Detection of resistance mutations
Early recurrence identification
Molecular Diagnostic Technologies
PCR
RT-PCR
FISH
Immunohistochemistry
Next Generation Sequencing (NGS)
Applications
Comprehensive genomic profiling.
Targeted Therapy
Precision Medicines
Examples:
Trastuzumab
Osimertinib
Imatinib
Alectinib
Dabrafenib
Benefits
Improved efficacy
Reduced toxicity
Personalized treatment
Precision Oncology
Concept
Matching therapy to molecular alterations.
Workflow
Patient → Molecular Testing → Biomarker Identification → Personalized Treatment
Benefits
Better outcomes and treatment selection.
Emerging Molecular Technologies
Innovations
Multi-omics
Single-cell sequencing
Spatial transcriptomics
Artificial Intelligence
Digital pathology
Future Impact
More precise cancer management.
Future Directions
Upcoming Advances
Early detection through blood tests
AI-driven diagnostics
Personalized vaccines
Gene editing
Advanced immunotherapies
Key Takeaways & Discussion
Key Messages
✓ Cancer is fundamentally a molecular disease
✓ Molecular biomarkers drive diagnosis and treatment
✓ Precision oncology is transforming cancer care
✓ Liquid biopsy and AI are shaping the future
✓ Personalized medicine improves patient outcomes
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