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88 Cards in this Set
- Front
- Back
The cells kill by releasing small cytoplasmic granules of proteins called?
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Perforin and Granzyme
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NK cells are activated by?
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interferon-γ
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Antibodies are recognized by ____ receptors on cells and phagocytes
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Fc receptors
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tumor-specific antigens (TSA) expressed by tumor cells but
not expressed by normal cells? |
Bcr-Abl
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Cancer caused by the Philadelphia Chromosome?
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chronic myelogenous leukemia (CML).
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CD8 cells must be activated by?
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Th or CD4 cells
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Tumor infiltrating lymphocytes (TILs) are mainly?
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cytotoxic T cells (Tc, CTLs, CD8+)
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Tumor cells display their own antigen on?
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MHC-I
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Regulatory T cells (T-regS)?
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CD4+ and CD25+
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Regulatory T cells inhibit both?
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inhibit both Th (CD4+, CD25-) and Tc (CTL, CD8+ CD25-) effector cells
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There is a strong correlation between the presence of _____ and the survival of patients with many cancers (e.g. ovarian, melanoma, breast,
colorectal) |
TILs
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TILs indicate a strong _______?
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Cellular response
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Tumor cells' primary mechanism of resistance?
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Decrease the expression of MHC-I
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Tumor cells secrete these cytokines to inhibit immunocytes?
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TGF-β and IL-10
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Four Immunity-Mediated Cancer Therapies?
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- immunostimulants (IFN-α, IL-2)
- cancer vaccines (in clinical trials) - adoptive T-cell transfer (in clinical trials) - monoclonal antibodies |
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MOA of Interferon-alfa (IFN-α)?
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stimulates cytotoxic activity of CTLs, NK cells and macrophages
• upregulates MHC class 1 and other surface markers |
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Major hurdle in adaptive T-cell transfer?
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establishment of stable population of reintroduced TILs in vivo
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What are the 5 classes of alkylating agents?
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1. nitrogen mustards
2. ethyleneimines 3. alkyl sulfonates 4. nitrosoureas 5. triazenes |
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What are the 6 nitrogen mustard agents?
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cyclophosphamide, ifosfamide, chlorambucil, mechlorethamine,
melphalan, bendamustine |
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What are the 2 most important nitrogen mustard agents?
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cyclophosphamide and ifosfamide
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Name the alkyle sulfonate alkylating agent?
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busulfan
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Name the triazene alkylating agents?
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dacarbazine and procarbazine
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Functional group of nitrogen mustard agents?
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bis-(2-chloroethyl)
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Mechanism of Alkylating Reaction of Nitrogen Mustard?
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Binding to the N7 position of guanine, causing interstrand cross-linakge
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Cyclophosphamide is used to treat?
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lymphoma, breast cancer, acute lymphocytic leukemia (ALL) and ovarian cancer
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Cyclophosphamide is a prodrug that makes the toxic metabolite _______?
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Acrolen
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Hemorrhagic cystitis caused by Cyclophosphamide can be counteracted by?
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Mesna (sulfonate) and diuresis
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Severe toxicity caused by Ifosfamide?
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CNS toxicity (crosses the BBB)
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Cell cycle effected by platinum complexes?
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Platinum complexes are cell-cycle non-specific
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Name the 3 platinum complexes?
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cisplatin, carboplatin and oxaliplatin
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Platinum complexes react with DNA forming intrastrand and interstrand cross-links, with N7 of guanine as the primary target. What is the favored cross-linking mechanism?
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Intrastrand
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Platinum complexes are cell-cycle non-specific, but they are most effective during ___phase
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S-phase
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Cisplatin causes nephrotoxicity that can be alleviated by?
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chloride diuresis and amifastine (Ethyol)
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pyrimidine analogs
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5-FU, capecitabine, cytarabine, gemcitabine, azacytidine,
decitabine |
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purine analogs
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6-mercaptopurine, fludarabine, pentostatin, cladribine,
clofarabine, nelarabine |
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Phase of cell cycle affected by antimetabolites?
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All antimetabolites are S-phase specific
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Primary MOA of MTX?
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inhibition of DHFR
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MTX toxicity can be rescued by?
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Leucovarin (folinic acid, N5-formyl FH4) a reduced folate coenzyme
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MOA of hydroxyurea?
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Inhibition of ribonucleotide reductase, thus blocking DNA synthesis
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MOA of 5-FU?
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blocks synthesis of TMP by inhibiting THYMIDYLATE synthase
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Agent that enhances the activity of 5-FU?
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Leucovarin
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MOA of purine analogs?
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inhibition of de novo synthesis of purine bases and nucleotides and as triphosphate derivatives incorporated into DNA strands
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MOA of vinca alkyloids?
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bind β-tubulin and block its ability to
polymerize with α-tubulin into microtubules |
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Vinca alkyloid metabolism?
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extensive hepatic metabolism by CYP3A4 requiring dose reduction
for hepatic impairment |
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Cell cycle phase affected by microtuble targeting agents?
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M-Phase
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MOA of taxanes (paclitaxel and docetaxel)?
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binding of β-tubulin subunit of microtubules and through the PROMOTION of microtubule polymerization
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Taxane moiety required for activity?
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C13 side chain on 8 member hexane ring
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Why does paclitaxel require a 50:50 Etoh to castor oil vehicle?
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Lipophilicity
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Method of correction for paclitexol lipophilicity?
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Abraxane: Paclitexol bound to albumin
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Topo-1 inhibitors?
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camptothecin analogs
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Camptothecin analogs?
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topotecan and, irinotecan
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Phase of cell cycle affected by topoisomerase inhibitors?
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S-phase
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Irinotecan (CPT-11) is a prodrug metabolized by hepatic
carboxylesterase to its active form ______. |
SN-38
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Topoisomerase II inhibitors?
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epipodophyllotoxins and anthracycline analogs
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Epipodophyllotoxins?
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Etopsode
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Anthracycline analogs?
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doxorubicin, daunorubicin, idarubicin
epirubicin, mitoxantrone |
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MOA of TOPO-II inhibitors?
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- flat 4-RING system intercalates directly with DNA (GC rich) forming a complex with topoisomerase and DNA, causing double-stranded DNA breaks leading to apoptosis. Also produces free radicals that damage DNA.
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All anthracyclines are _____toxic?
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Cardiotoxic
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3 reasons for the cardiotoxicity of anthracyclines?
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-quinolone reduction producing superoxide
-no catalase in cardiac tissue -high cardiac uptake of anthrcyclines |
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Ion chelator used to reduce the carditoxicity of anthracyclines?
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Dexarazoxone
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Liposomal anthracycline designed to reduce cardiotoxicity?
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Doxorubicin Liposomal (DOXIL)
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MOA of all-trans retinoic acid?
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-displacement of the repressor of differentiation
-promotion of the degradation of the PML-RARa fusion protein |
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MOA of arsenic trioxide?
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-displacement of the repressor of differentiation
-production of oxygen free radicals -inhibition of angiogenesis |
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Effect of ATR and ATRO on PML-RARa?
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ATO: Post translational modification of protein
ATRA: Replaces repressor and induces degradation (no post translational modification) |
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Aromatase inhibitors?
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Anastrazole - Breast
Exemestane -Breast Letrozole - Breast |
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SERD?
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Fulvestrant -Breast
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SERMs?
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Raloxifene - Breast
Tamoxifen - Breast |
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MOA of aromatase inhibitors?
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inhibits the enzyme aromatase, which is responsible for converting androgens to estrogens
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Androgen deprivation therapy?
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Goserelin acetate (Zoladex) is an injectable gonadotropin releasing hormone super-agonist (GnRH agonist), also known as a lutenizing hormone releasing hormone (LHRH) agonist. Goserelin acetate is used to suppress production of the sex hormones testosterone and oestrogen), particularly in the treatment of breast and prostate cancer.
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GnRH agonists?
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Leuprolide acetate and Goserelin acetate
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GnRH antagonist?
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Abarelix
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Androgen receptor blockers?
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Flutamide
Nilutamide Bicalutamide |
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Oral androgen deprivation agents?
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Flutamide
Nilutamide Bicalutamide |
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Rituximab?
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Anti-CD20 (Lymphoma)
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Alemtuzumab?
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Anti-CD52 (CLL)
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Gemtuzumab-Ozogamicin?
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Anti-CD33 + toxin (AML)
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Cetuximab?
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Anti-EGFR (colorectal cancer)
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Panitumumab?
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Anti-EGFR (colorectal cancer)
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Trastuzumab?
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Herceptin: anti-her2/neu (breast cancer)
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Bevacizumab?
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anti-VEGF (colorectal cancer)
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-ximab?
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Chimeric
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-umab?
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Humanized
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EGF-EGFR binding promotes?
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tumor cell growth and proliferation
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Suffix of tyrosine kinase inhibitors?
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-nib
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Tyrosine kinase inhibitors that inhibit ABL?
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Imatinib (CML, ALL)
Dastanib (Leukemia) Nilotinib (Leukemia) |
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Tyrosine kinase inhibitors that inhibit EGFR?
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Gefitinib (lung)
Erlotinib (lung) Lapatinib (breast) |
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Thalidomide complex?
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intercalates into DNA in G-C rich regions
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Bortezomib MOA?
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NF-Kb?
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