I. MOLECULAR BASIS OF BREAST AND OVARIAN CANCER
Key Oncogenic Pathways
- HER2 signaling pathway
- Estrogen receptor (ER) signaling
- PI3K–AKT–mTOR pathway
- DNA damage repair (BRCA-dependent homologous recombination)
- Angiogenesis (VEGF pathway)
Targeted therapy exploits abnormalities in these pathways.
II. TARGETED THERAPY IN BREAST CANCER
A. HER2-POSITIVE BREAST CANCER
HER2 (ERBB2) is a transmembrane receptor tyrosine kinase. HER2 amplification or overexpression leads to:
- constitutive signaling,
- increased proliferation,
- aggressive tumor behavior.
HER2 positivity occurs in ~15–20% of breast cancers.
Pathogenesis
- 1. HER2 gene amplification.
- 2. Overexpression of HER2 receptor.
- 3. Persistent activation of growth signaling pathways.
- 4. Increased tumor aggressiveness and recurrence risk.
HER2-Targeted Therapy
Monoclonal antibodies
- Bind extracellular HER2 domain
- Block receptor activation
- Promote immune-mediated tumor cell destruction
Tyrosine kinase inhibitors
- Inhibit intracellular kinase activity
- Block downstream signaling
Clinical Impact
- Dramatically improves survival
- Converts aggressive tumors into treatable disease
- Used in adjuvant and metastatic settings
B. HORMONE RECEPTOR–POSITIVE BREAST CANCER (Targeted Aspect)
Estrogen Receptor Signaling
ER-positive tumors depend on estrogen-mediated proliferation.
Targeted Pathway Modulation
Targeted agents are used to:
- block estrogen signaling,
- inhibit resistance pathways.
PI3K–AKT–mTOR Pathway
Pathogenesis
- 1. PI3K pathway activation via mutations.
- 2. Increased cell survival and proliferation.
- 3. Resistance to endocrine therapy.
Targeted Strategy
- Inhibition of pathway restores hormone sensitivity.