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Cancer Therapy

Cancer Chemotherapy & Targeted Cancer Therapy

Drug NameClassSpecifc
Leucovorin Methotrexate Rescue Treatment -> Bypass DHFR step in folic acid synthesis -> Rescue normal cells from undue toxicity
6-Mercaptopurine (6-MP) Antimetabolites/Purine pathway inhibitors -> Cell cycle S phase specific thus myelosuppression, diarrhea, mucositis -> 5 specific points -> Prodrug analog of natural purine hypoxanthine -> Oral bioavailability only 10-50% due to first-pass metabolism by xanthine oxidase in liver -> Hepatic elimination -> TPMT deficiency susceptible to severe toxicity -> Used to treat AML
Gemcitabine Antimetabolites/Pyrimidine pathway inhibitors -> Cell cycle S phase specific thus myelosuppression, diarrhea, mucositis -> 3 specific points -> Difluoro analog of deoxycytidine, converted from diphosphate to triphosphate inside the cells -> Good activity in solid tumors. -> Potent radiosensitizer
Cytarabine (Ara-C) Antimetabolites/Pyrimidine pathway inhibitors -> Cell cycle S phase specific thus myelosuppression, diarrhea, mucositis -> 4 specific points -> Incorporated into DNA and inhibits template function and chain elongation -> Most important antimetabolite used in AML therapy -> Inhibits ribonucleotide reductase (RNR) and incorporation of dCTP into DNA. -> IV only because cytidine deaminase in GI
5-Florouracil (5-FU) Antimetabolites/Pyrimidine pathway inhibitors -> Cell cycle S phase specific thus myelosuppression, diarrhea, mucositis -> 3 specific points -> Inhibits thymidylate synthase leading to thymidine depletion. -> Metabolized by the liver -> IV route preferred
Capecitabine Antimetabolites/Pyrimidine pathway inhibitors -> Cell cycle S phase specific thus myelosuppression, diarrhea, mucositis -> 2 specific points -> Oral prodrug of 5-FU -> Indicated in breast cancer and colorectal cancer.
Cyclophosphamide Alkylating Agents/Nitrogen mustards -> Non-cycle specific, myelosuppression! -> Alkylates guanine and changes base pairing to G-T -> Cells without p53 not undergo apoptosis (resistant) -> Resistance fast when used alone -> 4 specific points -> Requires metabolic activation in liver by P450 to 4-Hydroxycyclophosphamide -> Works by DNA crosslinking -> Major toxicity is myelosuppression -> Can lead to hemorrhagic ystitis
Mesna Cyclophosphamide Rescue Treatment Can save person's life
Melphalan Alkylating Agents/Nitrogen mustards -> Non-cycle specific, myelosuppression! -> Alkylates guanine and changes base pairing to G-T -> Cells without p53 not undergo apoptosis (resistant) -> Resistance fast when used alone -> 1 specific point -> Transported by the leucine transport uptake system.
Cisplatin Alkylating Agents/Platinum Compounds (-platin) -> Non-cycle specific -> Same manner as alkylating agents, formation of intrastrand and interstarand cross-links by N7 position of guanine. -> Enters by active Cu2+ transporter -> 3 specific points -> Indicated for metastatic ovarian and testicular cancer -> Dose-limiting nephrotoxicity -> High doses may cause progressive peripheral motor and sensory neuropathy.
Carboplatin Alkylating Agents/Platinum Compounds (-platin) -> Non-cycle specific -> Same manner as alkylating agents, formation of intrastrand and interstarand cross-links by N7 position of guanine. -> Enters by active Cu2+ transporter -> 1 specific point -> Major toxicity is strong myelosuppression
Oxaliplatin Alkylating Agents/Platinum Compounds (-platin) -> Non-cycle specific -> Same manner as alkylating agents, formation of intrastrand and interstarand cross-links by N7 position of guanine. -> Enters by active Cu2+ transporter -> 1 specific point -> Major toxicity is peripheral neuropathy. May be exacerbated by cold temperature.
Daunorubicin Cytotoxic antibiotics/Anthracylcines (-rubicin) -> Non-cycle specific -> Inhibit transcription by impairing topoisomerase and intercalating into DNA -> 3 specific points -> Administered IV -> Used for AML in combination with ara-C -> Limiting toxicity is delayed, cumulative cardiac toxicity.
Doxorubicin Cytotoxic antibiotics/Anthracylcines (-rubicin) -> Non-cycle specific -> Inhibit transcription by impairing topoisomerase and intercalating into DNA -> 1 specific points -> Limiting toxicity is delayed, cumulative cardiac toxicity.
Bleomycin Cytotoxic antibiotics/Antitumor Antibiotics (-mycin) -> Non-cycle specific -> Binds reduced iron & forms an intercalating complex with DNA -> 4 specific points -> Administered IV -> Minimal toxicity to bone marrow -> Reduced or impaired pulmonary function that may lead to pulmonary fibrosis -> Limiting toxicity is delayed, cumulative cardiac toxicity.
Dactinomycin (Actinomycin D) Cytotoxic antibiotics/Antitumor Antibiotics (-mycin) -> Non-cycle specific -> Binds reduced iron & forms an intercalating complex with DNA -> 3 specific points -> Dose-limiting hematopoietic suppression -> May be metabolized to produce a free-radical generating species -> Limiting toxicity is delayed, cumulative cardiac toxicity.
Vincristine Mitotic Inhibitors/Vinca Alkaloids -> M Phase specific -> Inhibition of tubulin polymerization disrupting assembly of microtubules. -> 2 specific points -> Peripheral neurotoxicity -> Treat pediatric leukemias and solid tumors
Vinblastine Mitotic Inhibitors/Vinca Alkaloids -> M Phase specific -> Inhibition of tubulin polymerization disrupting assembly of microtubules. -> 2 specific points -> Testicular carinoma, Nl & NHL. -> Neutropenia is the principal dose-limiting toxicity.
Paclitaxel Mitotic Inhibitors/Taxanes (-taxel) -> M Phase specific -> Promotes microtubule assembly and results in inhibition of mitosis and cell division. -> 2 specific points -> Hypersensitivity acute, and delayed peripheral sensory neuropathy -> Used in breast cancer
Docetaxel Mitotic Inhibitors/Taxanes (-taxel) -> M Phase specific -> Promotes microtubule assembly and results in inhibition of mitosis and cell division. -> 2 specific points -> Neurotoxicity is main side effect -> Used in breast cancer
Irinotecan Topoisomerase I Inhibitors (-tecan) -> S-phase specific agent -> 1 specific point -> Used primarily for refractory colorectal cancer
Etoposide Topoisomerase II Inhibitors (-poside) -> S and G2 specific agent -> 1 specific point -> Dose-limiting toxicity is myelosuppression
Imatinib Chemical Inhibitors/Protein kinase inhibitors (-nib) -> 2 specific points -> Used in ALL and CML caused by Bcr-Abl fusion protein (Philadelphia chromosome) -> Delayed side effect of fluid retention with ankle and periorbital edema, myelosuppression, GI
Erlotinib Chemical Inhibitors/Protein kinase inhibitors (-nib) -> 4 specific points -> Inhibits EGFR tyrosine kinase -> Metabolized by CYP3A4 -> Delayed side effect of interstitial lung disease -> Used for non-small cell lung cancer, pancreatic cancer
Crizotinib Chemical Inhibitors/Protein kinase inhibitors (-nib) -> 2 specific points -> Inhibits ALK and ROS1 inhibitor -> Used in ~4% of patients with non-small cell lung carcinoma who have chromosomal rearrangement of ELM4&ALK -> Side effects of rash, diarrhea, trail of lights phenomena
Everolimus Chemical Inhibitors/mTOR inhibitors (-limus) -> 1 specific point -> Lung or breathing problems, infections, kidney failure, delayed wound healing.
Temsirolimus Chemical Inhibitors/mTOR inhibitors (-limus) -> 1 specific point -> Fatigue, skin rash, stomatitis, hematologic abnormalities
Azacitidine Chemical Inhibitors/Epigenetic Pathway Inhibitors/DNA methylase inhibitors (DNMT) -> 3 specific points -> Can be incorporated into DNA and RNA strands -> Disassembly of polyribosomes & inhibition of the production of protein -> Myelosuppression, GI, skin side effects
Decitabine Chemical Inhibitors/Epigenetic Pathway Inhibitors/DNA methylase inhibitors (DNMT) -> 3 specific points -> Deoxy derivative of azacitidine -> Can only be incorporated into DNA strands -> Myelosuppression, GI, skin side effects
Vorinostat Chemical Inhibitors/Epigenetic Pathway Inhibitors/Histone deacetylase inhibitors (HDAC) -> 3 specific points -> Binds to active site of HDACs and results in accumulation of acetylated histones and acetylated proteins. -> Side effect of Edema -> First HDAC inhibitor
Bortezomib Chemical Inhibitors/Proteosome inhibitors -> 3 specific points -> First therapeutic proteasome inhibitor to be tested in humans -> Boron atom binds the catalytic site of the 26S proteasome. ->Peripheral neuropathy and GI side effects
Tamoxifen Hormone Therapy -> 5 specific points -> ALL pre-menopausal women with hormone receptor positive breast cancer -> Selective estrogen-receptor modulators -> Competitive inhibitor of estradiol binding to the ER -> Increased risk of endometrial cancer
Raloxifene Hormone Therapy -> 5 specific points -> Breast cancer in post-menopausal women -> Selective estrogen-receptor modulators -> Blood clots, leg swelling/pain -> Does not promote endometrial cancer or increase risk of cataracts
Anastrozole Hormone Therapy -> 4 specific points -> Breast Cancer ONLY post menopausal women! -> Non-steroidal aromatase inhibitor (inhibits the synthesis of estrogen) -> Arthralgias side effect
Abiraterone Hormone Therapy -> 2 specific points -> Prostate Cancer -> Androgen production inhibitor
Flutamide Hormone Therapy -> 3 specific points -> Prostate Cancer -> Antagonist of the androgen receptor -> Gynecomastia
Leuprolide Hormone Therapy -> 3 specific points -> Breast Cancer & Prostate Cancer -> Agonist at pituitary GnRH receptors -> Can cause bone pain
Prednisone Hormone Therapy -> 3 specific points -> Most commonly prescribed glucocorticoid in cancer therapy -> Converted to active prednisolone in the liver -> Inhibition of leukocyte infiltration at the site of inflammation.
ATRA (All-trans-retinoic acid) Hormone Therapy -> 3 specific points -> Derivative of vitamin A -> Used exclusive for acute promyelocytic leukemia (AML M3) -> Inhibits binding of PML-RAR on DNA and promotes transcription and differentiation of granulocytes. -> Retinoid acid syndrome: fever, wt gain, respiratory distress
Bevacizumab Immunotherapy -> 3 specific points -> humanized monoclonal antibody that targets all forms of VEGF-A -> Inhibits tumor vasculature -> Delayed symptom of arterial thromboembolic events
Trastuzumab (TDM-1) Immunotherapy -> 3 specific points -> antibody-drug conjugate -> Targets the HER2 protein with DM1 which is a microtubule destabilizing agent -> Fever & chills, weakness, headache, nausea
Cetuximab Immunotherapy -> 3 specific points -> Chimeric monoclonial antibody against the extracellular domain EGFR -> Binds EGFR and inhibits downstream signaling. Enhances response to chemotherapy and radiotherapy. -> Can cause acne-like skin rash
Rituximab Immunotherapy -> 3 specific points -> Monoclonal antibody against the protein CD20. -> Severe infusion reaction -> Leukemias and lymphomas
Ipilimumab Immunotherapy -> 3 specific points -> Human antibody that binds to CTLA-4 -> Blocks the CTLA-4 inhibitory signal allowing CTLs to destroy cancer cells -> Side effects of fever, rash, vitiligo, and colitis
Interferon-alpha Immunotherapy -> 2 specific points -> Increases major histocompatibility complex expression thus increasing immune effector T and natural killer cells. -> Malaise, fatigue, fever, worsen mood disorders
Interleukin 2 Immunotherapy -> 2 specific points -> Functions in proliferation of cytotoxic T-cells. Enhances T-cell response against cancerous cells. -> May lead to capillary leak syndrome.
Methotrexate Antimetabolites/Folate antagonists -> Cell cycle S phase specific thus myelosuppression, diarrhea, mucositis -> 4 specific points -> Inhibits dihydrofolate reductase (DHFR) -> Protein bound so other drugs can potientiate toxicity. -> Renal elimination -> Contraindications: impaired renal function! ascities, pleural effusions
Created by: carchase
 

 



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