Novel targets in cancer therapy Flashcards
3 organs systems usually affected by chemotherapy
- Mucositis (GI)
- Alopecia (Hair)
- Myelosuppression(BM)
Name 3 strategies for overcoming resistance
- Collateral sensitivity (resistance to one drug makes cell more sensitive to another drug)
- Combination therapy
- Dose escalation (w or w/o BM transplant)
- Constant infusion
- Adjuvant therapy
- Early detection
Difference between intrinsic, acquired, pharmacokinetic resistance, cytokinetic and cellular resistance
• Intrinsic: Resistance at onset of treatment
• Acquired resistance: Initially sensitive but then re-grow
• Pharmacokinetics (extracellular): systemic or tumor mass level
• Cytokinetic: Phase of the cell cycle inappropriate
• Cellular resistance: Increased genomic instability & mutations
o Mutation alternating drug target
o Enhanced drug metabolism efflux or DNA repair
o Decreased drug uptake or drug compartmentalization
o Overexpression of P-glycoprotein causes enhanced efflux (use Cisplatin, 5FU, AraC, cyclophosphamide or bleomycin instead)
o GST induction inhibits effect of cisplatin
o Failure to induce apoptosis: decreased expression of apoptosis proteins (Bax, Bcl-x)
Imatinib
Bcr-able
CML t(9,22) Gastrointestinal stromal tumors Inhibits tyrosine kinase domain of Bcr-Abl protein Cardiac toxicity
Trastuzumab
Her2/neu
Breast cancer (even estrogen resistant breast cancers)
Binds to Her2/neu receptor and prevents growth factor from binding
Cardiac toxicity
Dyspnea
Allergy
Erlotinib
EGFR (epidermal)
Lung cancers Non-small cell cancer Colorectal Metastatic Inhibits kinase portion of EGFR • Molecular resistance • Rash • Diarrhea • Dyspnea
Bevacizumab
VEGF Colorectal Colorectal Lung Blocks VEGF activity • Bleeding
Vemurafenib
V600 B-raf mutation Metastatic melanoma Inhibit serine-threonine kinase (BRAF) Arthralgia Skin rash Photosensitivity
