Chemotherapy Flashcards
Chemotherapy treatment intents
- Induction: complete remission
- Consolidation: increase cure rate, prolong remission
- Adjuvant: administer post-surgery to eliminate residual disease
- Neo-adjuvant: administered prior to surgery (shrink tumor)
- Palliative: control symptoms, prolong life, NOT curative
- Salvage: potentially curative, administered for recurrence
Explain the rationale for combination drug therapy.
• Goldie-Coldman hypothesis
o Maximal chance for cure occurs when all available agents are given simultaneously
o But side effects!
• Principles of combination therapy
o Select agents known to have single agent activity against disease
o Select agents with different mechanisms and toxicity profiles
o Administer at regular intervals
Describe the basis for cell phase selectivity.
- Cell phase specific = target cells in specific phase of replication
- Cell phase non-specific = target cells in any phase of division
List the major classes of anticancer agents
- Alkylating agents
- Antimetabolites
- Topoisomerase inhibitors
- Anti-mitotic agents
- Other DNA damaging agents
- Target specific inhibitors
Alkylating agents
o Cyclophosphamide
o Temozolomide
Antimetabolites
o 5-Fluorouracil
o Methotrexate
o Gemcitabine
Topoisomerase inhibitors
o Etoposide
o Irinotecan
Anti-mitotic agents
o Vincristine
o Paclitaxel
Other DNA damaging agents in Chemotherapy
o Bleomycin o Doxorubicin o Carboplatin o Cisplatin o Oxiplatin
Target specific inhibitors
o Cetuximab o Eriotinib o Gefitinib o Imatinib o Olaparib o Rapamycin o Rituximab o Sunitinib o Temsirolimus o Trastuzumab
Identify several mechanisms by which cancer cells develop resistance to cancer chemotherapy.
Primary resistance
o Genomic instability
o Mutation of p53 tumor suppressor gene
Acquired resistance
o Single agent resistance: genetic mutation imparting resistance to a single agent
o Multi-drug resistance mutation: MDR1 expression increasing p-glycoprotein an drug efflux
Name and describe the mechanisms of action of monoclonal antibodies
o Bind to antigens expressed on surface of malignant cells
o Block the growth of tumor and/or recruit the body’s immune system to attack the cancer cells
o Can be given as monotherapy, in combo with chemotherapy, and with other targeted therapies under the clinical trial
Structure:
• Fab: 2 fragments that allow Ab to bind to antigen
• Fc: cannot bind antigen, responsible for biological functions of the molecule once Fab binds antigen
Types:
• Unconjugated (more common)
• Conjugated: to radioisotopes, chemotherapy, toxins
Nomenclature:
• Momab: Ab from mouse
• Ximab: Ab that’s chimeric or a mixture of mouse and human
• Xumab or zumab: Ab that’s humanized
Name and describe the mechanisms of action of tyrosine kinase inhibitors
o Blocks binding of protein to receptor site → blocks signaling
o Cause decreases in cellular growth and proliferation by disrupting normal cell pathways
o Limits cancer growth
Name and describe the mechanisms of action of mTOR inhibitors
o Mammalian target of rapamycin (mTOR) signaling pathway functions as intermediary between variety of cell signaling events to regulate cell growth and cell proliferation and angiogenesis
o mTOR inhibitors = inhibit mTOR → cell cycle arrest
• Possible decreased expression of proteins like vascular endothelial growth factor (VEGF), PDGF, TGF and others involved in angiogenesis and cell growth
Name and describe the mechanisms of action of PARP inhibitors
Poly (ADP-ribose) Polymerase Inhibitors
Functions:
• Key role in repair of DNA single strand breaks through base excision repair pathway
• Binds directly to sites of DNA damage
• Recruits other DNA repair enzymes
• BRCA1 or BRCA2 deficiency sensitizes cells to PARP inhibition
