1. Anticancer agentSubmitted by:Kakadiya Dipesh

2. Content What is Cancer? Types of Cancer Causes and risk factors The Classification of AnticancerDrugs 3. What is Cancer?Cancer is a disease characterizedby uncontrollable, irreversible,independent, autonomous,uncoordinated and relativelyunlimited and abnormal overgrowth of tissues.Cancer spreads by invasion to thesurrounding tissues and bymetastasis to distant sites. 4. Types of Cancer Affected AreaAnal cancer AnusBreast Cancer BreastBladder Cancer Urinary BladderBone marrow Cancer Shafts of long bonesColon Cancer ColonCervical Cancer CervixEye Cancer EyeGynecological Cancer Female Reproductive organsLung Cancer LungOsteo sarcoma metaphyseal region of tubular long bonesWilms tumour KidneyLeukemia BloodLarynx Cancer LarynxTesticular cancer TestisRectal Cancer Rectum 5. Causes and risk factors:Environmentcigarette smoke chemicals UV light virusesMetabolic processesfree radicals DNA copying andrepair defects Inherited genetic mutations 6. The Classification ofAnticancer DrugsA. Drugs acting directly on cells(Cytotoxic drugs)1. Alkylating agents:o These compounds produce highlyreactive carbonium ion intermediateswhich transfer alkyl groups to cellularmacro molecules by forming covalentbonds.o Alkylation results in cross linking/abnormal base pairing/scission of DNA 7. Nitrogen mustardBreast cancer,Multiplemyelomahead and neck carcinomas,osteogenic sarcomaHodgkins disease,T-cell lymphomaChronic lymphocyticleukemiaMultiple myeloma,Ovarian cancer, Breastcancer 8. Recent drugs based on Nitrogen mustardBestrabucil (phase I trial)[Chlorambucil derivative]BendamustineUramustine (Nitrogen mustard+UracilDerivative) 9. EthylenimineAlkyl sulfonateOvarian cancer, BreastcancerLymphomaChronic MyeloidLeukemia 10. NitrosoureasTriazine:- meningeal leukaemias and brain tumours(cancross BBB)Malignant melanoma;Hodgkin's disease. 11. 2. Antimetaboliteso These are analogues related tonormal components of DNA or ofcoenzymes involved in nucleic acidsynthesis.o They competitively inhibit utilizationof the normal substrate or getthemselves incorporated formingdysfunctional macromolecules.o Several of the useful drugs used inantimetabolite therapy are purines,pyrimidines, folates, and related 12. Folate antagonistMethotrexate(NEOTREXATE)NHHNNOH2NCH2CH2Acute lymphoblastic leukemia,Lung cancer.ONH - CH -(CH2)2COOHCOOHPemetrexed 13. Purine antagonisto These are highly effective antineoplasticdrugs.oThey are converted in the body to thecorrespondingmonoribonucleotides which inhibit theconversion of inosine monophosphate toadenine and guanine nucleotides.NNNNHSH6-mercaptopurineNNNNHSHH2NThioguanineChildhood acute leukemia Adult acute leukemia 14. Recent drugs based on purines and related compounds:NNNNNH2ClOHOHOCladribineNNNNNH2OHOHOVidarabineOHNNNNNH2OHOHOClofarabineFClNNOHOHOPentostatinHNNOHNNNNNH2OHOOH FOOHHO POFludarabine 15. Pyrimidine antagonisto Pyrimidine analogues have variedapplications as antineoplastic, antifungal andantipsoriatic agents.HNONHOF5-Fluorouracil5-Fluorouracil is converted inthe body to the correspondingnucleotide 5-fluoro-2-deoxyuridine monophosphate,which inhibits thymidylatesynthase and blocks theconversion of deoxyuridilic acidto deoxythymidylic acid.This leads to elective failure ofDNA synthesis.Adenocarcinoma,Skin cancer 16. Recent drugs 17. 3. Natural anticancer agents:Vinca alkaloidso These are mitotic inhibitors, bind tomicrotubular protein-'tubulin', prevent itspolymerization and assembly of microtubules,cause disruption of mitotic spindle andinterfere with cytoskeletal function.o The chromosomes fail to move apartduring mitosis: metaphase arrest occurs.o They are cell cycle specific and act in themitotic phase. 18. Hodgkins disease,Acute lymphocyticleukemia,Lung cancer 19. Taxaneso First isolated frombark of Western /Pacific yew (TaxusobrIet visif oulsiae)d for treatmentof lung, ovarian ando Taxanes hyper-sbtarebailiszte csa mncicerro. tubulestructure (freez them). Taxanes binds to the subunit of tubulin ,the resultingmicrotubule/ Taxanes complex does nothave the ability to disassemble. Thisadversely affects cell function because theshortening and lengthening of microtubules 20. Ovarian cancer, Breast cancer,Non small cell lung cancerSemi-synthetic derivatives 21. EpipodophyllotoxinSmall cell lung cancer, Non-Hodgkinslymphomas,Kaposis sarcoma, Cervical cancerFrom PodophyllumpeltarumMay appleOOOOHMeO OMeOMeOPodophyllotoxinHOOOOOOOMeO OMeOHOEtoposideHOAffects DNAtopoisomerase II(notintercalating)DNA strandbreakageEtoposide (Semi-synthetic)Eposin EtopofosVepesid 22. Camptothecin analogueso First isolated Camptotheca acuminata(Chinese tree).o Inhibits DNA topoisomerase IIDNA strand breakageNNOOOH OCamptothecin,toxic, Lead comp.NNOOOH OHONNNOOOH ON OONTopotecanHycamtinIrinotecanCamptoSemisyntheticOvarian cancer, Small cell lung cancer 23. 4. Antibioticso These are products obtained frommicroorganisms and have prominentantitumour activity.o Practically all of them intercalate betweenDNA strands and interfere with its templatefunction.Actinomycin DWilms' tumour,Rhabdomyosarcoma 24. DoxorubicinMitoxantroneKaposis sarcoma,Small cell lung cancer,Breast cancer,Malignant lymphomasProstate cancer,Multiple sclerosis 25. DaunorubicinMitomycinKaposis sarcoma,Acute myeloid leukemiaCarcinomas of the cervix,Breast, lung, stomach 26. Recent anticancer antibiotics drugs:Calicheamicin(Priclinical) 27. Kigamicin C ( priclinical)Lactoquinomycin A 28. o 5. Miscellaneous :o These drugs have been developed byrandom synthesis and testing for anti tumouractivity.ProcarbazineHydroxyureaHodgkin's disease,Non-Hodgkin lymphomas,Oat cell carcinoma of lungChronic myeloid leukaemia,Psoriasis, Polycythaemia 29. CisplatinCarboplatinImatinibMetastatic testicularandOvarian carcinomaSquamous carcinoma ofheadand neck,Small cell lung cancer,Seminomachronic myeloidleukaemia 30. Recent drugsGefitinibErlotinibCrizotinibNon-SmallCell lungcancer(PROTEINKINASEINHIBITORS)OxaliplatinOvariancarcinoma,Seminoma 31. B. Drugs acting on Hormoneso It involves the manipulation of theendocrine system through exogenousadministration of specific hormones,particularly steroid hormones, or drugs whichinhibit the production or activity of suchhoorBmeocnaeuss.e steroid hormones are powerfuldrivers of gene expression in certain cancercells, changing the levels or activity of certainhormones can cause certain cancers to ceasegrowing, or even undergo cell death. 32. 1. Corticosteroids :o Corticosteroids are strong anti-inflammatorydrugs.o They are used to reduce swelling thatcauses cancer pain.Examples 33. Prednisolonepalliation of lymphomasand leukemiasDexamethasonehaematologicalmalignancies 34. 2. Estrogenso The agonist is occasionally used to treatprostate cancer through suppression oftestosterone production.FosfestrolcarcinomaprostateEthinylestradiol 35. 3. Selective estrogen receptormodulatorso Acts by selective antagonism of theestrogen receptor.BreastcancerToremifene Tamoxifen 36. 4. Selective estrogen receptor downregulatorso Estrogen receptor down regulators blocksthe effects of estrogen in breast tissue.FulvestrantMetastaticbreastcancer 37. 5. Aromatase inhibitorso Aromatase is the enzyme that synthesizesestrogen.o Aromatase inhibitors (AIs) are a class ofdrugs used in the treatment of breast cancerand ovarian cancer in postmenopausalwomen.o As breast and ovarian cancers requireestrogen to grow, Aromatase inhibitors aretaken to either block the production ofestrogen or block the action of estrogen on 38. LetrozoleAnastrozoleBreast cancerBreast cancer 39. ExemestaneEarly stage of breast cancerRecent drugAminoglutethimide Vorozole 40. 6. Antiandrogeno Antiandrogens, or androgen antagonists,first discovered in the 1960s, preventandrogens from expressing their biologicaleffects on responsive tissues.o Antiandrogens alter the androgen pathwayby blocking the appropriate receptors,competing for binding sites on the cell'ssurface, or affecting androgen production.o Antiandrogens are most frequently used totreat prostate cancer. 41. Flutamide BicalutamideNilutamide Finasteride 42. development status of antiandrogen drugs: 43. Recently Approved Drugs by FDADrugs Uses2014Belinostat Peripheral T-cell lymphomaRamucirumab Gastric cancerIbrutinib Chronic lymphocytic leukemiaIdelalisib Relapsed Chronic lymphocytic leukemiaCeritinib Non-small cell lung Cancer 44. Drugs Uses2013Obinutuzumab Chronic lymphocytic leukemiaAfatinib Metastatic non-small cell lung cancerIbrutinib Mantle cell lymphomaTrametinib Metastatic melanomaPomalidomide Relapsed and refractory multiple myelomaLenalidomide Mantle cell lymphomaRegorafenib Gastrointestinal stromal tumorDabrafenib Metastatic melanomaDenosumab Prostate cancer 45. References1. Wilson and Gisvold's textbook of organic medicinal andpharmaceuticalchemistry, Twelfth Edition, Charles Owens wilson, OleGisvold2. Essentials of Medical Pharmacology, Sixth Edition, K.DTRIPATHI3. Foyes Principles of medicinal chemistry, Sixth Edition,Thomas L.Lemke, David A. Williamshttp://www.fda.gov/drugs/informationondrugs/approveddrugs/ ucm279174.htm4.