Cancer Pharmacology (Part 1 of 2) Flashcards
What are oncogenes?
genes that positively influence tumor formation/ cell growth
what is an example of an oncogene?
Ras
what is a tumor suppressor gene?
genes that negatively impact tumor growth
what is an example of a tumor suppressor gene?
p53
how would you know whether a gene is an oncogene or a tumor suppressor?
oncogenes promote cell growth while tumor suppressor genes slow growth
the majority of cells in our bodies are at what phase of the cell cycle?
G0 “resting”
what is the purpose of cell cycle checkpoints?
they control transitions between cell cycle stages
what is being checked at cell cycle checkpoints?
is there DNA damage? is there spindle assembly? are there favorable conditions? is there completed replication?
what happens if there is failure to pass a cell cycle checkpoint?
the cell cycle is delayed or cell apoptose
aberrations in checkpoint regulation result in what?
uncontrolled and unregulated cell proliferation
activation of oncogenes has what result?
it overrides G1 arrest
inactivation of tumor suppressor genes has what result?
overrides G2 arrest
what are the indications for primary chemotherapy?
when the cancer is advanced, no alternative treatment exists, or it is an advanced metastatic disease
primary chemotherapy can cure some cancers- what are they?
hodgkin’s and non-hodgkin’s lymphoma, choriocarcinoma, germ cell cancer, and AML
what is neoadjuvant chemotherapy?
the use of chemotherapy in patients who present with localized cancer for which alternative local therapies, such as surgery, exist, but which have been shown to be less than completely effective
what is the goal of neoadjuvant chemotherapy?
to reduce the size of the primary tumor
what is adjuvant chemotherapy?
when additional chemotherapy is given for a defined period of time after surgery–> helps to prevent relapse
what are the goals of adjuvant chemotherapy?
to reduce the incidence of local and systemic recurrence
what is tissue growth fraction?
the ratio of proliferating to G0 cells
as a general rule, antineoplastic agents are more effective on?
cells with a high growth fraction; and they will impact noncancerous high growth cells
what are some examples of cells with high growth fraction?
cells of the bone marrow, GI tract, hair follicles, and sperm-forming cells
what is one significant determinant of responsiveness to chemotherapy?
the growth fraction
as the tumor burden increases, what happens to the growth fraction and the doubling time?
the growth fraction decreases and the doubling time increases
the initial growth rate of most solid tumors is what?
rapid but decreases over time
why is a low growth fraction in tumors challenging?
because chemotherapy will have minor activity
the growth fraction of solid tumors can be increased how?
by reducing the tumor burden (i.e. surgery or radiation)
what does the log cell kill hypothesis allow us to better understand?
the impact of the effect that a single dose has on the cancer cells: it’s a fraction of cells rather than an absolute number- so in each individual treatment, you can expect to kill a fraction of the cells that are remaining
antineoplastic therapy follows what kinetics? and what does this mean?
first-order; this means that a given dose of drug destroys a constant fraction of cells
what is the approach to the eradication of cancer like?
it is a step-wise approach
what are common routes of administration of antineoplastic drugs?
IV and PO
what are the benefits of alternative routes of administration of antineoplastic drugs?
they can reduce systemic toxicity and increase drug delivery (by avoiding pharmacologic sanctuaries)
what are pharmacological sanctuaries?
regions where tumor cells are less susceptive to antineoplastic agents
what are some examples of alternative routes of administration of antineoplastic drugs?
intracavity, intrathecal, intraventricular, intraarterial, topical, and isolated limb perfusion
combination drug therapy is more successful than single-agent regimens; what are the advantages of combination chemotherapy?
it provides maximal cell killing within the range of tolerated toxicity; it is effective against a broader range of cell lines in a heterogenous tumor population and it may delay or prevent the development of drug-resistant tumors
what is primary/inherent chemotherapeutic resistance?
drug resistance in the absence of prior exposure to available standard agents
what is the main contributor to primary/inherent chemotherapeutic resistance?
the genomic instability (i.e. p53 mutations)
what is acquired chemotherapeutic drug resistance?
develops in response to exposure to a given cancer chemotherapeutic drug
what genetic change is occurring in cases of acquired chemotherapeutic drug resistance?
amplification or suppression of a particular gene
how does the increasing heterogeneity of cancers over time affect treatment plan?
as the different cell lineages within the cancer cell changes, it affects our ability to kill and target those cancers
what is p-glycoprotein (PGP) and where is it expressed?
it is expressed in tissues with barrier functions, such as the kidneys, liver, and GI tract; it does a really good job of taking drugs that are inside the cell and kicking them out
what does a high baseline expression of PGP correlate with?
correlates with primary/inherent resistance to natural products; PGP can also be over-expressed leading to acquired drug resistance
many antineoplastic agents are mutagens themselves- what does this mean? and give an example
they can give rise to neoplasms years after treatment (e.g. alkylating agents have cause AML and ALL)
what are common adverse effects of antineoplastic agents?
nausea, vomiting, fatigue, stomatitis, and alopecia; myelosuppression, low sperm count, and depressed development of exposed children
what can myelosuppression lead to?
can lead to impaired wound healing and predisposition to infection
what agents are used as rescue agents for neutropenia, thrombocytopenia, and anemia?
hematopoietic agents
what agents are used as rescue agents for emetogenic effects?
serotonin receptor antagonist (ondansetron)
what agents are used as rescue agents to delay skeletal complications?
bisphosphonates
