- structurally related to folic acid - MTX inhibits dihydrofolate reductase (DHFR) which converts folic acid to its active form - poor CNS penetrations

Oncology Flashcards by JOSH WOHL

susceptibility and growth cycle

The fraction of tumor cells that are in the replicative cycle influences their susceptibility to most cancer chemotherapeutic agents
Rapidly dividing cells are generally more sensitive
Slowly proliferating cells less sensitive
Nonproliferating cells usually survive

How well did you know this?

Not at all

Perfectly

cell cycle specificty

Normal cells and tumor cells go through growth cycles
Cell-cycle specific - chemotherapeutic agents that are effective only against replicating cells
Cell-cycle nonspecific - useful against tumors that have low percentage of replicating cells (still have more toxicity in cycling cells)

How well did you know this?

Not at all

Perfectly

growth rate

Initially rapid in most solid tumors
Decreases as tumor size increases
Unavailability of nutrients and oxygen due to inadequate vascularization and lack of blood circulation
Surgery or radiation can reduce burden promoting remaining tumor cells into proliferation, increasing susceptibility to chemo agents

How well did you know this?

Not at all

Perfectly

treatment protocols

combination chemotherapy is more successful than single-drug treatment in most cancers

How well did you know this?

Not at all

Perfectly

Generally interfere with the availability of normal purine or pyrimidine nucleotide precursors
Inhibiting their synthesis
Competing with them in DNA or RNA synthesis

antimetabolites

How well did you know this?

Not at all

Perfectly

MTX

structurally related to folic acid
MTX inhibits dihydrofolate reductase (DHFR) which converts folic acid to its active form
poor CNS penetrations

How well did you know this?

Not at all

Perfectly

6-Mercaptopurine (6-MP) MOA

Nucleotide formation
Penetrates target cells and is converted to 6-thioinosinic acid (TIMP)
Inhibits first step of purine-ring biosynthesis
Blocks formation of AMP and xanthinuric acid
TIMP converted to thioguanine monophosphate (TGMP) which after phosphorylation can be incorporated into RNA and DNA
Results in nonfunctional RNA and DNA
-does not cross BBB

How well did you know this?

Not at all

Perfectly

ADR of 6-MP

1/3 of patients report hepatotoxicity in the form of jaundice

How well did you know this?

Not at all

Perfectly

6-Thioguanine (6-TG)

Converted intracellularly to TGMP

MOA similar to 6-MP

How well did you know this?

Not at all

Perfectly

Fludarabine

Purine nucleotide analog

Decreases synthesis in S phase and affects function

How well did you know this?

Not at all

Perfectly

ADR of fludarabine

High doses, progressive encephalopathy, blindness and death

How well did you know this?

Not at all

Perfectly

cladribine

Purine analog
Similar reactions to fludarabine
Hinders elongation and repair of DNA
Potent inhibitor of ribonucleotide reductase
-distributes through CSF

How well did you know this?

Not at all

Perfectly

5-Fluorouracil (5-FU)

Pyrimidine analog
Deprives cell of thymidine decreasing DNA synthesis
Administered with leucovorin to increase effectiveness
-crosses BBB

How well did you know this?

Not at all

Perfectly

ADR 5-FU

“hand-foot syndrome” – erythematous desquamation of the palms and soles

How well did you know this?

Not at all

Perfectly

Capecitabine

Undergoes enzymatic reactions after being absorbed that results in 5-FU

How well did you know this?

Not at all

Perfectly

how to tx a 5-FU or capecitabine OD

Uridine Triacetate

How well did you know this?

Not at all

Perfectly

floxuridine

Analog of 5-FU

Catabolized in the liver to 5-FU

How well did you know this?

Not at all

Perfectly

Cytarabine (ara-C)

Pyrimidine antagonist

-does not cross BBB

How well did you know this?

Not at all

Perfectly

gemcitabine

Analog of deoxycytidine

How well did you know this?

Not at all

Perfectly

trifluridine and tipiracil

thymidine-based nucleoside analog
incorporated into DNA, interferes with DNA synthesis and inhibits cell proliferation
Tipiracil -Thymidine phosphorylase inhibitor
Inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase

How well did you know this?

Not at all

Perfectly

dactinomycin

Intercalates into the minor groove of the double helix forming a dactinomycin-DNA complex
Interferes primarily with DNA-dependent RNA polymerase
At high doses will hinder DNA synthesis
Causes single-strand breaks
-does not penetrate CNS

How well did you know this?

Not at all

Perfectly

doxarubicin/daunorubicin

Free radicals induce membrane lipid peroxidation, DNA strand scission and direct oxidation of purine or pyrimidine bases, thiols and amines
-does not penetrate CNS

How well did you know this?

Not at all

Perfectly

ADRS of doxarubicin

cardiotoxic

stomatitis

bleomycin

Mixture of different copper-chelating glycopeptides that cause scission of DNA by oxidation

Cell-cycle specific
Causes cells to accumulate in the G2 phase

ADR of bleomycin

pulmonary

Mechlorethamine

Once transported into the cell, forms a reactive intermediate that alkylates a guanine residue in one or both strands of a DNA molecule

Cyclophosphamide and Ifosfamid

Biotransformed in liver to hydroxylated intermediates which are then broken down to phosphoramide mustard and acrolein -cross BBB

ADRs of cyclophosphamide and ifosfamid

Germ cells Amenorrhea, testicular atrophy, aspermia, sterility Veno-occlusive disease of the liver ~25% of patients

nitrosureas (carmustine, lomustine, streptozocin)

Alkylation that inhibits replication and RNA and protein synthesis Primarily cytotoxic to actively dividing cells Nondividing can escape if DNA repair occurs Inhibit key enzymatic processes by carbamoylation of amino acids -cross BBB

Dacarbazine/Temozolomide

Undergoes biotransformation through CYP450 to become active – methyltriazenoimidazole carboxamide (MTIC) -crosses BBB

Cell-cycle and phase specific Block mitosis in metaphase (M phase) Binds tubulin and prevents formation of microtubules

vincristine/vinblastine

Active in G2/M phase of the cell cycle | Bind irreversibly to the β- tubulin subunit

paclitaxel/docetaxel

Estrogen antagonist

tamoxifen

Inhibits adrenal and extra-adrenal synthesis, aromatase inhibitor

Aminoglutethimide

Imidazole aromatase inhibitors

anastrozole/letrozole

Steroidal, irreversible inhibitor of aromatase

exemastane

Occupy GnRH receptor in pituitary, inhibiting release of FSH and LH

leuprolide, goserelin

Inhibit growth of prostatic tissue by blocking LH production

estrogens

Synthetic, nonsteroidal antiandrogens

Flutamide, Nilutamide, Bicalutamide

Converted in vivo to abiraterone, an androgen biosynthesis inhibitor, that inhibits 17 α-hydroxylase/C17,20-lyase

abiraterone actetate

Androgen receptor inhibitor

enzalutamide

Induces complement and antibody dependent , cell-mediated cytotoxicity of B cells Often used in combo such as cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)

rituximab

CD20-directed cytolytic antibody

Obinutuzumab

Antiangiogenesis agent

bevacizumab

Believed to target the epidermal growth factor receptor on cancer cells, inhibiting growth

cetuximab

reversible proteasome inhibitor | preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome

ixazomib

Binds guanine in DNA forming inter- and intrastrand cross-links Inhibits DNA replication and RNA synthesis

Cisplatin, Carboplatin, Oxaliplatin | does not penetrate CNS

mammalian target of rapamycin (mTOR) inhibitor MTOR is a serine/threonine protein kinase that regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, autophagy, and transcription

everolimus

kinsase inh end in

nib

Target topoisomerase II Block cells in late S to G2 phase Irreversible double-strand breaks

Etopside and Teniposide

Catalyzes deamination of asparagine to aspartic acid and ammonia

L-asparaginase

hedgehog pathway inhibitor Hedgehog (Hh) is an intercellular signaling molecule essential for normal embryonic development and plays critical roles in adult tissue maintenance, renewal and regeneration

vismodegib | "gib"

histone deacetylase (HDAC) inhibitor

belinostat | "stat"

inhibitor of BCL-2, an antiapoptotic protein

venetoclax

poly (ADP-ribose) polymerase (PARP) inhibitor | PARP enzymes play a role in DNA repair

rucaparib | "parib"

a CD19-directed genetically modified autologous T cell immunotherapy

Tisagenlecleucel

genetically modified oncolytic viral therapy | replicate within tumors and to produce the immune stimulatory protein GM-CSF

Talimogene Laherparepvec