General Concepts Lapinsky Flashcards
What does unfixable DNA damage result in?
apoptosis
What does fixable DNA damage result in?
cell continues dividing
What are combination drug regimens chosen for?
Clinical efficacy
Drug synergy
Target cells with different drug resistance mechanisms
Target cells at different stages of replication
Why is drug synergy important?
allows use of lowest effective dose to decrease toxicities and side effects
What is drug synergy?
2 or more drugs are combined to produce an effect greater than the sum of their individual separate effects
Why is chemo administered in cycles?
allows the patients to recover from side effects
What are cell cycle specific drugs (CCS)?
kill cancer cells during a specific phase of the cell cycle
What drug classes are examples of CCS?
Anti-metabolites (s phase)
Anti-mitotics (m phase)
What are cell cycle nonspecific drugs (CCNS)?
kill cancer cells in ANY phase of the cell cycle including G0
What drug classes are examples of CCNS?
DNA alkylating/ platinating agents, anthracyclines
Traditional cytotoxic cancer therapeutic agents are more effective at killing cells that are actively undergoing ______ _________
cell division
What is the rate theory of cancer chemotherapy?
cancers characterized by more rapid cell division are more susceptible to the cytotoxic effects of traditional cytotoxic chemotherapy
Besides rapidly dividing cells, what are some cancer agents designed to recognize?
- Specific biomarkers present on the surface of cancer cells (HER2 + breats cancer cells)
- Other cells that are essential for cancer cell growth (monoclonal antibodies)
What is the G0 phase of cell division?
a resting phase that can occur after mitosis/ cell division
What is the G1 phase of cell division?
post-mitotic phase where cells grow and prepares to replicate DNA
What is the s phase?
DNA synthesis/ replication
What is the G2 phase?
pre-mitotic phase where the cell grows and produces RNA and proteins to prepare for cell division
What is the m phase?
mitosis; parent cell divides into 2 daughter cells
Liquid tumors tend to have a ______ growth factor
high
Solid tumor tend to have a _______ growth factor
low
What types of drugs are least effective at treating tumors with low growth factors? Why?
CCS drugs; most cells are in G0
What type of drugs only kill proliferating cells, rapidly increasing in number?
CCS drugs
What type of drugs kill proliferating and nonproliferating cells?
CCNS
What type of drugs kill both low and high growth-fraction tumor cells?
CCNS
What type of drugs kill high growth fraction tumor cells?
CCS
What type of drugs are considered “schedule dependent” both timing and duration matter?
CCS
What type of drugs are considered “dose dependent”?
CCNS
What is the lower limit of cancer cell detection?
1 billion cells
What is the log-kill hypothesis?
1-g tumor treatment with anticancer drug results in 3log kill/ 1log survive
Why is it important to know the MOA of individual anti-cancer agents?
reduce overlapping toxicities
reduce drug resistance
Why are CCNS drugs usually given before CCS drugs (recruitment schedule)?
achieve a significant log kill with CCNS drug, when cells are recruited back into the cell cycle use CCS to kill dividing cells
When would a recruitment schedule not be used?
When CCNS drug prevents inactivation metabolism or elimination of the CCS drug leading to CCS drug toxicity
What is an example of a recruitment schedule?
3 days of Daunorubicin + 7 days of Cytarabine
What is an irreversible state of cell dormancy?
Cell senescence
