Alkylating agents
- transfer alkyl groups to various cellular constituents
- general MOA involves intramolecular cyclization forming an ethylene imonium ion that may directly or through formation of a carbonium ion transfer an alkyl group to a cellular constituent
Antimetabolites
have similar chemical structure to essential substances in the cell and interfere with utilization of these substances which adversely affects cell function and growth
Anti-tumor antibiotics
bind to DNA through intercalation between specific bases and block the synthesis of RNA, DNA, or both
Treatment strategies
- Surgery
- Radiotherapy
- Chemotherapy
Primary chemotherapy
Chemo is the only thing that can be helpful
Neoadjuvant chemotherapy
prior to surgery to reduce tumor size
Adjuvant chemotherapy
after surgery
Combination chemotherapy
multiple drugs used
Why use combo therapy
- Way to get around resistance
- Increase cell kill while limiting toxicity (Do not want to overlap toxicity- do not double down on cardio-toxic effects)
Models of cell kinetics
- murine
- gompertzian
Murine
-exponential cell growth; so there is a constant faction of cells being killed instead of a certain number
Gompertzian
- slow in beginning, increases exponentially and then plateaus
- tumor will proliferate rapidly until it gets to a certain size, this will cause more cells to stay in G0
What cell cycle phase do anticancer cancer agents inhibit?
- Antimetabolites
- Vinca Alkaloids
- Bleomycin
- Taxanes
Antimetabolites: S phase
Bleomysin: G2 phase
Vinca alkaloids and taxanes: M phase
Agents not cell cycle specific
- Alyklating agents
- MAB
- TK receptor inhibtors
- Anthro-cyclines
Mechanisms of anti-cancer drug resistance
-P53- tumor suppressor gene: If mutated, unable to suppress cell cycle
-Anti-metabolites: Methylate DNA and cross link DNA so that it cannot be replicated and cancer cells can resist
by increasing the amount of enzyme that degrades anti-cancer therapeutic of blocking enzyme that would turn on medication
Treatment for Hodgkins lymphoma
- Blemoycin
- Doxorubicin
- Vinca alkaloids
- Decarbazine
Blemoycin
- anti-tumor antibiotic w/ pulmonary toxicity
- Binding to DNA, which results in single- and double-strand breaks following free radical formation, and inhibition of DNA biosynthesis
Doxorubicin
- Oxygen free radicals bind to DNA causing single- and double-strand DNA breaks; inhibits topoisomerase II; intercalates into DNA; w/
- Cardio toxicity (all anthro cyclines)
- Rescue therapy: dexresosan which inhibits generation of free radicals- before
Vinca alkaloids
-Micro-tubule de-stabalizer, from periwinkle plant, toxicity Nausea, vomiting, allopecia,
Breast Cancer
- Trestuzamab
- Cyclophosphamide (alkylating agent)
- Tamoxifen
- Anastrozole
- Methotrexate (anti-metabolite)
Trestuzamab
HER2 receptor blocker
Cyclophosphamide (alkylating agent)
- Great bio-availability
- Hemorrhagic cystitis: Metabolite (acarlyn) is toxic to bladder because it is excreted through urine
- Rescue therapy: mesna; Prior- not after, because it prevents from happening but does not help with symptoms after it occurs
Tamoxifen
- SERM: antagonist for estrogen receptor. Given for years
Anastrozole
- aromatase inhibitor; Given for years
