Anti-Cancer Drugs

  1. What is CCS?
    Cell cycle-specific- not active against resting cells (Go phase)
  2. What is CCNS?
    Cell cycle-nonspecific- can sterilize tumor cells regardless of whether tumor cells are cycling or resting in Go phase.
  3. Can CCNS drugs kill both Go and cycling cells?
    Yes, although cycling cells are more sensitive.
  4. What type of cancers are CCS drugs most effective against?
    CCS drugs are most effective against hematologic cancers and solid tumors in which a large portion of cells are proliferating or are in the growth fraction.
  5. What type of cancers are CCNS drugs useful in treating?
    CCNS drugs (bind to and damage DNA) are useful in low growth fraction solid tumors and high growth fraction tumors.
  6. What does all effectivie CCS and CCNS drugs inactivate?
    Tumor stem cells (which are only a small fraction of the cells in a tumor.

    Non-stem cells (tumor cells that have irreversibly differentiated)are considered sterile (harmless).
  7. CCS agents:
    • Antimetabolites
    • Bleomycin
    • Epipodophyllotoxins
    • Taxanes
    • Epothilones
    • Vinca Alkaloids
  8. CCNS agents:
    • Alkylating Agents
    • Anthracyclines
    • Dactinomycins
    • Mitomycins
    • Camptothecins
  9. What are the two major types of Resistance to Anticancer drugs?
    • 1. Primary Resistance
    • 2. Acquired Resistance
  10. What is Primary Resistance?
    Primary Resistance is the absence of response to cancer chemotherapy on the FIRST EXPOSURE to a cancer drug.

    This type of inherent resistance has been attributed to the genomic instability associated with development of most cancers.
  11. What is Acquired Resistance?
    Acquired Resistance develops in DRUG-SENSITIVE TUMORS.

    Acquired Resistance can be caused by:

    • 1. highly specific against a single drug due to alterations in the genetics of the tumor with amplification or increased expression of one or more specific genes.
    • 2. Multidrug Resistance (MDR):

    • a) MDR attributed to increased expression of the normal MDRI gene (For cell surface glycoprotein invovled in drug efflux. P-glycoprotein- transport molecule, requires ATP to expel a variety of foreign molecules from cell.)
    • b) Overexpression of the Multidrug Resistance Protein 1 (MRP1)- MRP1 is a ATP-binding transmembrane transporter, increases resistance of natural product anticancer drugs by acting as export pump.
  12. Can MDR be reversed?
    • Yes, MDR can be reversed by administering drugs that:
    • -inhibit efflux transporters, such as calcium channel blockers
  13. What are the toxicities of anticancer drugs?
    -Toxicities related to the rate of cell growth


    -Toxicities UNrelated to the rate of cell growth
  14. What are the toxicities of anticancer drugs that are related to the rate of cell growth?
    • 1. Bone marrow depression (Myelosuppression)- due to damage of normal erythropoietic/leukopenic cells
    • 2. Nausea, vomiting, diarrhea - damage to epithelial cells o the GIT
    • 3. Alopecia- damage to hair-follicle cells (hair loss)
  15. What are the classes of Polyfunctional Alkylating Agents?
    • -Bis(chloroethyl)amines
    • (cyclophosphamide, mechlorethamine, chorambucil, Melphalan)
    • -Nitrosoureas
    • (Carmustine, Lomustine, Semustine)
    • -Aziridines
    • (Thiotepa, Triethylenemelamine)
    • -Alkylsulfonates
    • (Busulfan)
    • -Other related drugs
    • (Procarbazine, Dacarbazine, Altretamine, Cisplatin, Carboplatin, Ozaliplatin)
  16. Antimetabolites?
    • -Methotrexate
    • -Pralatrexate
    • -Purine Antagonist
    • (6-Thiopurines, Fludarabine phos, Cladribine)
    • -Pyrimidine Antagonists
    • (Fluorouracil, Capecitabine, Cytarabine, Gemcitabine)
  17. Natural Products?
    • -Vinca Alkaloids
    • (Vinblastine, Vincristine, Vinorelbine)
    • -Epipodophyllotoxins
    • (Etoposide, Teniposide)
    • -Camptothecins
    • (Topotecan, Irinotecan)
    • -Taxanes
    • (Paclitaxel, Docetaxel)
    • -Epothilones
    • (Ixabepilone)
    • -Anthracyclines
    • (Doxorubicine, Daunorubicin, Idarubicin, Epirubicin)
    • -Mitoantrone
    • -Dactinomycin
    • -Mitomycin
    • -Bleomycin
  18. Hormonal agents?
    • -Antiandrogens
    • (flutamide, bicalutamide, nilutamide)
    • -Antiestrogen
    • (Tamoxifen, Raloxifene, Fulvestrant)
    • -Adrenocorticosteriods
    • (hydrocotrisone, prednisone)
    • -Progestins
    • (Megestrol acetate)
    • -Gonadotropin-Releasing Hormone Agonists
    • (Leuprolide, Goserelin, triptorelin)
    • -Gonadotropin-Releasing Hormone Antagonists
    • (Degarelix)
    • -Aromatise Inhibitors
    • (Aminoglutethimide, Anastrozole, Letrozole, Exemestane)
  19. Protein Tyrosine Kinase Inhibitors?
    • Imatinib
    • Dasatinib
    • Sunitinib
    • Sorafenib
    • Gefitnib
    • Erlotinib
    • Lapatinib
    • Nilotinib
    • Temsirolimus
    • Everolimus
    • Pazopanib
  20. What is the Mechanism of Action for Alkylating Agents?
    • -CCNS
    • -cytotoxic effects via transfer of their alkyl groups to various cellular constituents, akylation of DNA and other cell components leading to cell death
    • -intramolecular cyclization to form an ethyleimonium ion that transfer an alkyl group to a cell constituent
    • -Major site of alkylation within DNA is the N7 position of guanine (other bases are also alkylated to lesser degree)
    • -Covalent Binding interactions between drug and DNA through cross-linking (Can be single strand (Monofunctional alkylating agents) or both strands (Bifunctional alkylating agents))
  21. Which has a higher efficacy? Bifunctional alkylating or monofunctional alkylating agents, and why?
    Bifunctional alkylating agents have a higher efficacy, compared to monofunctional alkylating agents, because of their ability to cross-link DNA (more).
  22. What does Alkylation of DNA results in?
    Miscoding or Excision of alkylated residues; leads to DNA strand breakage
  23. What are the mechanisms of Acquired Resistance to Alkylating Agents?
    • 1. Increased capability to repair DNA
    • 2. Decreased cell permeability to the drug
    • 3. Increased production of glutathione (inactivates the electrophilic alkylating agent via conjugation)
    • 4. Increased glutatione S-transferase activity (enzyme that catalyzes the glutathione conjugation reaction)
  24. Does Cross Resistance exist among alkylating agents?
    Yes, cross resistance exsits among alkylating agents. However, there are exceptions to the rule, depending on the specific type of tumor.
  25. What are the most common toxicities of the alkylating agents?
    nausea, vomiting, and bone marrow depression
  26. Which is the Most Widely used Alkylating Agent?
    Cyclophosphamide- administered ORALLY
  27. What does Cyclophosphamide require?
    Cyclophosphamide requires activation to its cytotoxic form by cyt. P450 enzyme system in the liver.

    -it is a less reactive alkylating agent
  28. Where does the active metabolites of cyclophosphamide delivered to?

    How does the liver protect itself?
    Active metabolites of cyclophosphamide are first delivered to both TUMOR and NORMAL tissue, where nonenzymatic cleavage of aldophosphamide to the cytotoxic forms (electrophiles- phosphoramide mustard and acrolein)

    The liver protects itself from the cytotoxic effects by further metabolizing the active metabolites to inactive ones.
  29. What does the Antimetabolites act on, and take advantage of?
    The antimetabolites act on intermediary metabolism of proliferating cells.

    They take advantage of a number of quantitative differences in metabolism that exist between neoplastic cells and normal cells. (These differences make tumor cells more susceptible to this class)
  30. What is the Mechanism of Action for Antimetabolites?

    -prevents the biosynthesis or utilization of normal cellular metabolites

    -structurally related to metabolites and cofactors invovled in biosynthesis of nucleic acids

    -B/c of similar structures, antimetabolites can antagonize the normal cell metabolites and cofactors, thus inhibiting nucleic acid synthesis

    -Many antimetabolites are ENZYME inhibitors

    -Some antimetabolites have to be bioactivated
  31. How does the Antimetabolites inhibit enzymes?
    • 1. Binding to the catalytic site of the enzyme- compete with the normal substrate due to structural similarity
    • 2. Binding to an allosteric regulatory site - particularly when antimetabolite is struct. similar to the END PRODUCT of a pathway (feed back control)
  32. Methotrexate:
    • -Antimetabolite, CCS
    • -Folic acid antagonist- binds to active catalytic site of dihydrofolate reductase (DHFR) enzyme, inhibiting the enzyme and interfacing with the synthesis of tetrahydrofolic acid (THF)
    • -Inhibits formation of DNA, RNA, and proteins (Lack of THF inhibits thymidylate, purine nucleotides, amino acids serine, methionine)
    • -Intracellular formation of Polyglutamate derivatives are selectively retained in cancer cells and increas the inhibitory effects on the enzymes invovled in folic acid synthesis, increases the duration of action of methotrexate.
  33. Tumor cell resistance to Methotrexate has been attributed to?
    • 1. Dec. drug transport into cell
    • 2. Dec. polyglutamate formation
    • 3. Synthesis of increased levels of DHFR via gene amplification
    • 4. Altered DHFR with reduced affinity for methotrexate
    • 5. Active efflux through activation of a MDR P170 glycoprotein transporter
  34. What are the major toxicities of Methotrexate?
    Bone marrow depression- leucopenia and thrombocytopenia
  35. Methotrexate also inhibits synthesis of purines and DNA in normal cells.

    What is used to reverse this effect and how does it work?
    Leucovorin is administered to "rescue normal cells". Leucovorin is an intermediate in the biosynthesis of purines and DNA.

    • Leucovorin prevents lethal effects of methotrexate by:
    • -rescueing biosynthesis of DNA and purines (By passes the folate reductase step in normal cells)
    • -inhibits active transport of methotrexate into normal cells
    • -Stimulates Efflux of methotrexate out of normal cells (Methotrexate does not accumulate in normal cells)
  36. Why does Leucovorin NOT rescue tumor cells?
    Leucovorin does NOT reach adequate levels in tumor cells and as a result will not rescue tumor cells.
  37. What is Mercaptopurine (6-MP)?
    -Antimetabolite, CCS
  38. What is the Mechnism of Action for Mercaptopurine (6-MP)?
    -must be bioactivated by hypoxanthine-guanine phosphoribosyl transferase (HGPRT) to form 6-thioinosinic acid

    6-thioionosinic acid inhibits enzymes invovled in purine nucleotide interconversions (DNA synthesis inhibited)
  39. What is the commom Resistance to Mercaptopurine?
    • -Decrease in HGPRT(hypoxanthine-guanine phosphoribosyl transferase) activity
    • -increased levels of alkaline phosphatase which inactivates 6-MP
  40. Major Toxicities for Mercaptopurine:
    myelosuppression and hepatotoxicity
  41. What is the importance of a reduced dose of Mercaptopurine in pateints also taking Allopurinol?
    6-MP is inactivated by xanthine oxidase enzyme into 6-thiouric acid.

    Allopurinol is an inhibitor of xanthine oxidase.

    Allopurinol enhances activity and toxicity of 6-MP.
  42. What is Allopurinol used for?
    treats hyperuricemia (INC uric acid) in chemo patients.

    Allopurinol inhibits xanthine oxidase, which is the enzyme which inactivates mercaptopurine.

    A REDUCED dose of mercaptopurine should be administered to patients to reduce toxicity from 6-MP.
  43. What is Fluorouracil?
    -Antimetabolite, CCS
  44. What is the Mechanism of Action for Fluorouracil?
    -must be bioactivated into ribosyl and deoxyribosyl nucleotide metabolites

    -affects DNA and RNA mediated events

    -bioconverted into flurodeoxyuridine monophosphate (fDUMP)- inhibits thymidylate synthase and synthesis of thymidylate (inhibits DNA synthesis)

    -bioconverted inot fluroridine triphosphate (FUTP)- incorporates into RNA (interferes with RNA processing and mRNA translocation)
  45. Major Toxicities of Fluorouracil (5-FU)?
    myelosuppression and neurotoxicity
  46. What are the two important Vinca Alkaloids?
    Vinblastine, Vincristine

  47. What is the Mechanism of Action of the Vinca Alkaloids?
    -cause depolarization of microtubules (imprt in cytoskeleton and mitotic spindle)

    -they BIND to microtubules protein TUBULIN in dimeric form. Drug-tubulin complex terminates assembly and depolymerization of the microtubules

    -Depolymerization of microtubules results in mitotic arrest at metaphase (Mphase), dissolution of the mitotic spindle, and interference with chromosome seperation
  48. What are the major toxicities of Vinblastine?
    - nausea, bone marrow depression, alopecia

    (Vinblastine is a vinca alkaloid)
  49. What is the dose-limiting toxicity for Vincristine?
    Neurotoxicity is the major dose-limiting toxicity for vincristine.

    myelosuppression can occur, but milder and much less significant than vinblastine.
  50. What is Epipodophyllotoxins?

    Mechanism of Action?

    -CCS, (Etoposide, Teniposide)

    -BLOCKS cell division in late S-G2 phase of cell cycle

    -Inhibit TOPOISOMERASE II, results in DNA damage through strand breakage

    -Major Toxicities: nausea, vomiting, alopecia, bone marrow depression
  51. What is Camptothecins?


    (Topotecan, Irinotecan)

    • -CCNS
    • -Inhibit TOPOISOMERASE I (enzyme responsible for cutting and religating single DNA strands)

    -leads to DNA damage

    -Toxicities: nausea, vomiting, diarrhea, myelosuppression, arthralgias (joint pain)
  52. What are Taxanes?


    (Paclitaxel, Docetaxel) -CCS

    -mitotic spindle poisons through high affinity binding to microtubules with enhancement of tubulin polymerization

    -promotion of micotubule assmebly by taxanes leads to inhibition of mitosis and cell division

    • -Toxicities: paclitaxel- arrhythmias, bone marrow depression, peripheral sensory neurophathy
    • docetaxel- neurotoxicity, neutropenia
  53. What are Epothilones?
    • -CCS
    • -cytotoxic macrolides derivatives
    • -Ixabepilone- semisynthetic epothilone, treats breast cancer
  54. What is the Mechanism of Action for Epothilones (Ixabepilone)?
    -binds to tubulin of microbules to induce microtubule polymerization and stabilization

    -leads to arrest of cells in G2-M phase of cell cycle (induces apoptosis)

    Epothilones and Taxanes bind DIFFERENTLY to tubulin b/c they are NOT structurally related.

    Epothilones are NOT affected by the common mechanisms of resistance to the taxanes (NO cross resistance)

    Ixabepilone is active against tumors that are resistance to paclitaxel.
  55. What are some common toxicities in Ixabepilone?

    -peripheral sensory neuropathy and neutropenia
  56. What are the Anthracyclines?
    • -CCNS
    • -among most widely used
    • -Daunorubicin, Doxorubicin - first agents in class
  57. What is the Mechanism of Action for the Anthrocyclines?
    • 1. Inhibition of Topoisomerase II
    • 2. High-affinity binding to DNA through INTERCALATION- inhibit DNA and RNA, and DNA strand breakage
    • 3. Binding to cellular membranes- alters fluidity and ion transport
    • 4. Generation of semiquinone free radicals and oxygen free radicals
  58. What is a special feature of the structures of Anthracyclines?
    Anthracyclines have some aromatic rings that make part of their structure FLAT. Easier to 'intercalate' between the DNA strands.

    intercalate -insert themselves between DNA bases
  59. What are the major toxicities of Anthracyclines?
    myelosupression with neutropenia, cardiotoxicity
  60. What causes the major cardiotoxicity in Anthracyclines?

    What are the two types of cardiotoxicities?
    Generation of free radicals cause cardiotoxicity

    • 1. Acute Cardiotoxicity: occurs first 2-3 days of therapy, arrythmias and myocarditis, usually transient, asymptomatic in most cases
    • 2. Chronic Cardiotoxicity: dose-dependent, cardiomyopathy associated with heart failure, caused by INC FREE RADICALS with in myocytes.
  61. How can you reduce cardiac toxicity with Anthracyclines?
    • 1. decrease dose
    • 2. use of continous, slow infusion rate
    • 3. use with Dexrazoxane (Zinecard)- zinecard chelates IRON and DEC. Free Radical production
  62. What are Mitomysincs?


    -CCNS alkylating agents

    -activated via enzymatic reduction to form an alkylating eletrophile species that cross links DNA

    -Hypoxic tumor cells exist in enviorment conducive to reduction reactions, and are more sensitive to mitomycin than normal cells and oxygenated tumor cells.

    -Toxicities: thrombocytopenia, leucopenia
  63. What are Bleomycins?
    • -CCS, accumulates cells in G2 phase
    • -Bleomycin is a peptide, has DNA-binding region and Iron-binding domain

    -Binds to DNA, results in single strand and double strand breaks, free radicals forms, leads to inhibition of DNA synthesis

    -Fragmentation of DNA is due to oxidation of DNA-bleomycin-Fe (II) complex, leads to chromosomal aberrations
  64. What is the major toxicity with Bleomycins?
    dose-limiting toxicity is pulmonary toxicity.

    characterize by pneumonitis with cough, dyspnea, and infiltrates.

    incidence inc. with age(>70 yrs old), and with cumulative doses >400 units
  65. What are SERM's and what are the two major SERM's?
    SERMs- Selective estrogen-receptor modulator--acts as partial agonists. agonist in certain tissues, while antagonists in other tissues

    Tamoxifen and Raloxifene

    Hormonal Agents- used to treat breast cancer
  66. What are the differences between Tamoxifen and Raloxifene?
    Both are SERMS

    Tamoxifen- estrogen agonist in bone and uterus. estrogen antagonist in breast

    Raloxifene- estrogen antagonist in uterus and breast
  67. Tamoxifen:
    anti-estrogen, useful in treatment of early-stage and metastatic breast cancer.

    also used as chemopreventative agent in high risk women for breast cancer

  68. Tamoxifen vs. Raloxifene:
    Both indicated for and equally effective in prevention of breast cancer in women at high risk

    Raloxifene may have more favorable adverse-effect profile, fewer thromboembolic events and less uterine hyperplasia when compared to tamoxifen
  69. Mechanism of Action (Tamoxifen)
    • -competitive partial agonist of estrogen
    • -binds to estrogen receptors of estrogen-sensitive tumors

    -longer halflife(7-14 days)than estradiol

    -ten fold affinity for estrogen receptor than estrodiol, indicates ablation of edogenous estrogen for optimal antiestrogen effect.
  70. Drug Interactions of Tamoxifen
    - Tamoxifen is bioactivated by CYP2D6

    -Inhibitors of CYP2D6 such as SSRI may LOWER effect of Tamoxifen in preventing recurrence of breast cancer

    -SSRI is common in women taking Tamoxifen, both to treat depression and decrease hot flashes

    • -SSRI- potent inhibitors of CYP2D6 are Fluoxetine and Paroxetine
    • Sertraline inhibits CYP2D6 to a LESSER extent

    -SSRI's- Citalopram and Excitalopram are weak inhibitors of CYP2D6, and are the safest choice for women who need SSRI with Tamoxifen therapy
  71. Toxicities for Tamoxifen
    Tamoxifen is well tolerated.

    toxicities are mild: menopausal symptoms, thromboembolic events (DVT, pulmonary embolism)

    Tamoxifen therapy increases risk/incidence of estrogen-sensitive endometrial hyperplasia and cancer.
  72. What are SERDs?

    Which drug is a SERD?
    SERDs- Selective estrogen-receptor downregulator- do not have any estrogen-agonist activities

    SERDs- pure anti-estrogen, pure ER-antagonists

    SERDs- better safety profile, faster onset, longer duration than SERMs

    FULVESTRANT- treat postmenopausal women with hormone receptor-positive metastatic breast cancer that has progressed despite first-line anti-estrogen therapy (tamoxifen).
  73. What is the Mechanism of Action for Fulvestrant?
    -a steroidal anti-estrogen that binds to the estrogen receptor with affinity more than 100 times that of tamoxifen (almost irreversible binding)

    -binding of fulvestrant to ER, sterically hinders receptor dimerization, leading to inhibition of receptor dimerization and INC in ER degradation (turn over).

    -Fulvestrant reduces the number of ER molecules in cells

    -ER downregulation abolishes ER-mediated transcription, completely supressing the expression of estrogen-dependent genes. (explains why fulvestrant is effective against tamoxifen-resistant breast cancer)
  74. Fulvestrant toxicities?
    generally well tolerated

    most common adverse effects: nausea, vasodialation (hot flashes), headache
  75. What are the Antiandrogens?
    Nonsteroidal antiandrogens- used to treat early-stage and metastatic prostate cancer

    --BINDS to the androgen receptor of androgen-sensitive tumors and BLOCKS androgen effects

    Flutamide- common antiandrogen

    -used in combination with radiation therapy

    Toxicity: mild nausea, hot flashes, gynecomastia, decreased libido and potency
  76. GnRH Agonists (Gonadotropin-Releasing Hormone)
    Major types: Leuprolide, Goserlin, Triptorelin

    • -synthetic peptides analogs of GnRH
    • -function as GnRH agonists, more potent than natural hormone
    • -stimulate transient release of follicule-stimulating hormone (FSH) and luteinizing hormone (LH), followed by INHIBITION of the release of FSH and LH
    • --leads to supression of testosterone production in testes
    • - in men, 2-4 weeks of GnRH agonist, results in castration levels of testosterone
    • -treat advanced prostate cancer and part of neoadjuvant therapy of early stage prostate cancer
  77. What is one complication of GnRH agonist therapy?
    • There is a transient flare of disease which results from initial surge of LH and FSH
    • -can be avoided by temporary (2-4 weeks) administration of androgen receptor blockers or use of GnRH Antagonists.
  78. Major toxicities of GnRH agonists?
    hotflashes, impotence, gynecomastia

    inc. risk of diabetes and heart disease
  79. What are GnRH Antagonists?
    • Degarelix
    • -synthetic decapeptide GnRH receptor antagonist- used for rapid meidcal castration of med with advanced prostate cancer

    • -binds reversibly to the GnRH receptor in anterior pituitary glad
    • -inhibits release of gonadotropins (LH and FSH)
    • -suppresses testosterone production in testes

    -GnRH antgonist therapy rapidly reduces serum testosterone levels w/out transient initial surge observed with GnRH agonist therapy. (no other advantage)

    Toxicities: hot flashes, weight gain, increased hepatic transaminases

    -Long term androgen deprivation therapy can prolong QT interval
  80. What are Aromatase Inhibitors?
    Aromatase enzymes converts the adrenal androgen androstenedione to estrone [androgen into estrogen] (occurs in body fat)

    Anticancer aromatase inhibitors- inhibit estrogen synthesis in adipose tissues and treats breast cancer in postmenupausal women

    (since estrogen promote growth of breast cancer, extrogen synthesis in adipose tissue can be important in breast cancer growth in postmen. women)
  81. What is the Mechanism of Action for Aminoglutethimide?
    -Aromatase Inhibitor

    • -nonsteroidal inhibitor of aromatase enzymes
    • -inhibits extrogen synthesis in adipose tissues
    • -inhibits adrenal steriodogenesis
    • -normally administered with hydrocortisone to prevent adrenal insufficiency

    -Toxicities: adrenal insufficiency and myelosuppression
  82. What is the Mechanism of Action for Anastrozole?
    • -Aromatase Inhibitor
    • --Letrozole is similar to Anastrozole

    • -Selective Nonsteroidal inhibitor of aromatase
    • -No inhibitory effect on adrenal glucocorticoid or mineralocorticoid synthesis (unlike Aminogluthemide-has affect on adrenal)

    -used to treat postmen. women with metastatic breast cancer that is ER-positive, women whose tumor have progressed while on tamoxifen, also used as adjuvant therapy of post men women with hormone-positive, early stage breast cancer

    Toxicities: mild nausea, hot flashes, arthralgias
  83. What is the Mechanism of Action for Exemestane?
    -Aromatase Inhibitor

    -steroidal hormonal agent

    -binds and irreversibly inactivates aromatase enzymes

    • -NO cross resistance between Exemestane and the nonsteriodal aromatase inhibitors
    • -treat advance breast cancer in postmen women, when tumor still progress with tamoxifen

    -toxicities: mild nausea, headache, hot flashes
  84. What is Imatinib?
    Imatinib is a Protein Tyrosine Kinase Inhibitor

    inhibits platelet-derived growth factor receptro (PDGFR) tyrosine kinase, the cytoplasmic ABL tyrosine kinase, and the receptor tyrosine kinase KIT.

    -treats cancers which the ABL, KIT, or PDGFR have dominate roles in driving tumor proliferation (mutation results in constitutive activation of kinases)

    -therapeutic efficacy in chronic myelogenous leukemia (CML), gastrointestinal stromal tumors (GISTs), chronic myelomonocytic leukemia (CMML), and hypereosinophilic syndrom (HES)


    -Aquired Resistance: mutations in the kinase domain

    -Adverse effects: nausea, vomiting, edema, muscle cramps
  85. What are Protein Kinases?
    -critical components of signal transduction pathways, transmit information, extracellular or cytoplasmic conditions to nucleus, influences gene transcription and/or DNA synthesis
  86. What are tyrosine kinases?
    -classified into proteins that have an extracellular ligand binding doman (receptor tyrosine kinases) and enzymes that are confined to the cytoplasm and/or nuclear cellular compartment (nonreceptor tyrosine kinases)

    --Abnormal activation of specific protein tyrosine kinaes are present in human cancers- molecular targets for cancer therapy
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Anti-Cancer Drugs
Cancer Drugs