Anticancer Drugs INTRODUCTION Cancer is a disease of cells characterized by progressive, pe and uncontrolled proliferation of tissue, Cancer cell produce oncoproteins [cPat-2020] Clinically available anticancer drugs act by cell growth inhibitor. [GATE-1997] Lung’s cancer is the most common cancer in men. Breast cancer is most common cancer in women. The genes most commonly affected in hereditary breast and ovarian cancer are the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) genes. Breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2). [GPAT-2018] Genetic change -—00-38 — 668° Normal cell Cancer cell| Doublin, Benign tumor rent, abnormal, purposeless the absence of growth factor or external stimuli. Tumor cells Normal cells EEN * Growslowly and have distinct borders + Do notinvade surrounding tissue * Do not invade other parts of the body + eg. Fibroids in the uterus and lipomasin the skin RUNNER * Can grow quickly and have irregular borders * Often invade surrounding tissue Can spread to other parts of the body through a process called metastasis - CarcinomaRES nd PE CARCINOMA. Carcinomas are abnormal cells that divide without control. ‘They ate able to spread to other parts of the body. SARCOMA Cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue- LEUKEMIA Cancer that starts in blood-forming tissue such as the bone caevow and causes large numbers of abnormal blood cells to be produced and enter the blood. e immune system. Cancers that begin in the cells of th: LYMPHOMA AND MYELOMA CENTRAL NERVOUS Cancers that begin in the tissue of the brain and spinal SYSTEM CANCERS cord. GERM CELL CANCER Germ cell, Testicle, and ovarian cancers. BLASTOMS Resemble embryonic tissue. Italso called Hodgkin disease, is a type of cancer that HODGKIN'S LYMPHOMA. develops in the lymph system. NON-HODGKIN'S itis a type of cancer that begins in your lymphatic system, LYMPHOMA. which is partof the body's germ-fighting immune system. Q CAUSES OF CANCER + Biological Factors + Occupational and Environmental Factors Social and Psychological + Chemicals in Food “Viral Factors * Medical Factors Subscribe Our sores Ss = 1b) Ey Scan QR’ code MOLT ate Mahathon Senics GaY Gos toes Caer Ra tas] oeegencnanin oainigaion | 7 coun | Siniapeiageaion | Bele, OTT Thiol “COC CLASSES App ope DCCLASSES Maye rend hes) aCHEMOTHERAPY OF NEOPLASTIC DISEASE : ANTICANCER DRUGS NERS PHASES OF CELL CYCLE |] Both normal as well as cancerous cells must pass through the following phases of cell cycke Gi phase (Presynthetic phase) | Synthesis of enzymes and other cellular Longest phase (6-12 hours) __| compounds needed for DNA synthesis, S phase (Synthesis phase) DNA synthesis takes place. (6-Bhours) Gz Phase (Premito icphase) | Synthesis of cellular components for (3-4hours) mitosis (Proteins & RNA Synthesis). M Phase (Mitotic phase) Mitotic cell division take place. Shortestphase (1 hours) Go Phase (Resting phase) Cell stops dividing temporarily or permanently. O ANTICANCER DRUGS MAY BE DIVIDED INTO TWO GROUPS 1. Cell cycle specific (ccs) * Act mainly in dividing cell 2. Cell cycle non-specific (CCNS) Act mainly in dividing cell as well as resting cell. A Rhea Aes DRUGS CTA S CoA Tat To tie) Gy Etoposide ‘ALKYLATING AGENT (Longest phase) * Melphalan s ANTIMETABOLITE + Cyclophosphamide * Methotrexate * Nitrosoureas * 6- mercaptopurine PLATINUM COMPOUND "= S-flurouracil * Cisplatin = Capecitabine = Carboplatin = Cytarabine + Oxaliplatin = _Cytosine arabinoside [GATE-2005]_] ANTHRACYCLINS G TOPOISOMERASE INHIBITOR * Doxorubicin = Irinotecan * Daunorubicin = Topotecan * Epirubicin = Etoposide + Mitoxantrone = Bleomycin MITOMYCINS C M VINCA ALKALOIDS = Dactinomycin (Shortest phase) | * Vincristine + Camptothecin [GPAT-2023] * Vinblastine * Vinorelbine ‘TAXENES * Paclitaxel [GPAT-2013] + Docetaxelsex GPAT DISCUSSION CENTER, avons Makes Side Ee ] CLASSIFICATION’ OF ANTICANCER DRUGS _ 1. Alkylating Agents yhamide, fosphamide, Nitrogen mustards Mechlorethamine, Cyclophosp! Chlorambucil, Melphalan, Benda [GATE-1998,GPAT-2010,2022] Thiotepa, Altretamine Busulfan [GPAT-2022] Carmustine, Lomustine Dacarbazine, Temozolomide Procarbazine Z. Platinum coordination complexes Cisplatin, Carboplatin, Oxaliplatin 3. Antimetabolites Methotrexate, Pemetrexed [GATE-1995, 4997,GPAT-2023] &-Mercaptopurine (6-MP), 6-Thioguanine (6-76), ‘Azathioprine, Fludarabine [GATE-1997] =-Fluorouracil (5-FU), cytarabine, Capecitabine, Doxyfluridine [GATE-1997] mustine Ethyleneimine Alkyl sulfonate Nitrosoureas Triazine Methyl hydrazine Folate antagonist Purine antagonist Pyrimidine antagonist Gemcitabine, 7. Microtubule damaging agents Vincristine, Vinblastine, Vinorelbine Paclitaxel, Docetaxel Vinca alkaloids [GPAT-2023] ‘Taxanes 5. Topoisomerase-2 inhi Etoposide, Teniposide 6. Topoisomerase-1 inhibitors | Topotecan, Irinotecan 7. Antibiotics ‘Actinomycin D (Dactinomycin), Doxorubicin, Aclarubicin, Epirubicin, Daunorubicin (Rubidomycin), Mitoxantrone, Bleomycin, Mitomycin C, Idarubicin, Epirubicin [GPAT-2014] Hydroxyurea, ‘Arsenic trioxide, L-Asparaginase, Tretinoin 8. Miscellaneous 1._| BCR-ABL tyrosine kinase inhi Imat 2. ] EGF (HER) receptor inhibitors Gefitinib, Erlotinib, Cetuximab, Trastuzumab, Lapatinib tors Bevacizumab, Sunitinib, Sorafenib 3._| Angiogenesis inh ‘4,_| Proteasome inhibit Bortezomib 5._| CD20 inhibitors Rituximab Tagwaltcom | © BOOTHs7e%e, © 97TeTESEEO awatond the app) rs ow clctepatcom | Ncedee “GDC CLASSES" App (Type GDC CLASSES in Py put Dacenton Crater Pou HS. Dowelfo Oct Prednisolone, (others) 3 Fosfestrol, Ethinyl estradiol 2. s 3. | Selective Estrogen Receptor Tamoxifen, Toremifene Modulators (SERMs) 4 trogen Receptor Down | Fulvestrant gulators (SERDs) 5,_[ Aromatase inhibitors Letrozole, Anastrozole, Exemestane 6._[ Antiandrogen Flutamide, Bicalutamide 7._| 5-« reductase inhibitor [GPAT-2011] | Finasteride, Dutasteride Nafarelin, Triptorelin, Leuprorelin logues s 8.__[GnRNa Hydroxyprogesterone acetate 9. | Proges Ae ee Daunorubicin) [GPAT-2015] 2.__[ Busulphan, Bleomycin Pulmonary fibrosis Vincristine, Vinblastine, Vinorelbine Peripheral neuropathy 4. | Methotrexate [GPAT-2017] Megaloblastic anaemia, Hepatotoxicity, Obstructive nephropathy Haemorrhagic cystitis, Alopecia, SIADH 5. | Cyclophosphamide, Ifosfamide [GPAT-2014] 6. | Cisplatin Emesis, Nephrotoxicity, Neuropathy, Ototoxicity [GPAT-2016] 7. | 5-Flourouracil, Capecitabine, Fludarabine, Cytarabine Hand and foot syndrome, Neurotoxicity 8._ | 6- Mercaptopurine, 6-Thioguanine | Hepatotoxicity *9,_| Paclitaxel, Vincristine Peripheral neuropathy, Hypersensitivity 10._| Docetaxel Peripheral neuropathy, Fluid retention 11. | Irinotecan, Gemcitabine Diarrhoea 12. | Doxyfluridine Bone marrow depression, Hearing loss, Neuritis 13._[Cytarabine Cerebral ataxia (neurotoxicity) 14. [Chlorambucil Lymphatic leukaemia NOTE - Natural anticancer agents: - Vinca alkaloids: Vincristine, Vinbkstine, Vinorelbine Epipodophyllotoxin: Etoposide, Teniposide Taxanes: Paclitaxel, Docetaxel Antibiotics: Anthracycline (Doxorubicin, Epirubicin, Daunorubicin), Bleomycin, Mitomycin-C Camptothecin: Topotecan, Irinotecan Enzymes: L asparaginase STS" App (Type GDC CLASSES in laystore o Dovoload{PAT DISCUSS! BEE I cyToroxic DRuGS J] O ALKYLATING AGENTS © Allalkybting agents have alkyl group(s)- = They abo have radiomimette effect (like ionizing radiation). hey get converted to Aziridinium ions and bind to 7® position -N atom of guanine of DNA base pairs. ‘Alkylating Agents Form highly reactive carbonium ion Transfer alkyl groups to nucleophilic sites of DNA bases Results in DNA strand breakage (Alkylating agents can also bind damage them) Cross linkage ‘Abnormal base pairing (Inhibiting DNA (Alkylated guanine base pairs with replication) thymine rather than cytosine and results to protein and in production of defective protein) {cell proliferation + Alkylating agents can ako bind to proteins and damage them. Mechlorethamine « Itis the first nitrogen mustard; highly reactive and local vesicant. © Itis one of the drugs useful for the treatment of Hodgkin's disease. Cyclophosphamide « Cyclophosphamide is a prodrug converted to the active metabolite Aldo phosphamide in the liver. © Active metabolite of Cyclophosphamide is 4-hydroxyl cyclophosphamide. [GATE-1993] . > Adverse effect © Haemorrhagic cystitis, Bone marrow suppression. [GATE-2001, GPAT-2014] Pancytopenia, Alopecia. Ifosfamide It is an analog of cyclophosphamide. Actions and toxicities similar to cyclophosp! It causes Hemorrhagic cystitis like cyclophosphamide but it i hamide except it is longer-acting. s less myelotoxic and less emetogenic than cyclophosphamide. Mesna is given with Ifosfamide (1-2 g). is excreted in urine - binds and inactivates the vasicotoxic metabolites of ifosfamide and * Mesna cyclophosphamide. [GPAT-2023] Gput Disonloa Center PLA. | ww. la, www detgpnt.om | ‘Dowaload “GDC CLASSES" App (Type GDC CLASSESinERAPY OF NEOPLASTIC DISEASE : ANTICANCER DRUGS Ey [—* Phosphamide Meta mustard. 7 C¥totoxic effect Cyclophosphamide ——+ Aldophoshamide—| Toxic metabolite + Acrolein ——» (Damage kidney blood Mesna (2-mercaptoethane Sulphonate) vessels) Mesna. i Binds with cyclophosphamide and Ifosfamide (SH = | compound) w+ Ssemonate‘ses tse toxicity Melphalan + Itisa phenyl alanine derivative. + Analkylating agent add an alkyl group to DNA. + Itattaches the alkyl group to the guanine base of DNA, at the number 7 nitrogen atom of the imidazole ring. * Common toxicity bone marrow depression. SCAN ME Chlorambucil ‘geet + Avery slow acting alkylating agent * A drug of choice for lymphatic leukaemia. a Mechanism of Action + Interfering with DNA replication and damage the DNA cell * Chlorambucil alkylates and cross-links DNA during all phases of the cell cyck, including + DNA damage via three different methods of covalent adduct generation with doubk helical DNA. Adverse effect - Pulmonary fibrosis Busulphan + Itdepresses bone marrow with selective action on myeloid series. + It was the preferred drug for chronic myeloid leukaemia (CML). Nitrosoureas + Carmustine and Lomustine are highly lipid soluble drugs * They cross BBB - effective in meningeal leukaemia and brain tumour. * Visceral fibrosis and renal damage can occur. Dacarbazine * Itis triazine derivative. [GPAT-2015] * Primarily inhibit RNA and protein synthesis. * After activation in liver, the active metabolite methylates the DNA and interfere with its function * Used for malignant melanoma and Hodgkin's disease. Q NOTE A melanoma is a tumour produced by the malignant transformation of melanocytes. [GPAT-2022] To scannaTe44, oTTOTOSCHGrae Discus OE ns Sty Q PLATINUM COORDINATION COMPLEXES Cisplatin : : © Itisa heavy-metal complex with highly effective antincoplastic activity. + Cisphtin isadministered intravenously. ctrates BBB and fs slowly excreted in urine, + Itpoorly p nism of Action Forms highly reactive Reacts with DNA (Forms both interstrand platinum complexes and interstrand cross-links) Mech: DNA damage Uses: * Very powerful against testicular cancer * Also useful in the treatment of Bladder, Ovary, Head and Neck carcinoma, + Adverse effect + Renal tubular damage, ototoxicity, and Peripheral neuropathy. + Hypokalaemia, hypocalcaemia and hypomagnesaemia * Cisplatin has mutagenic, teratogenic and carcinogenic properties. Carboplatin * Carboplatin is a less toxic derivative of cisphtin. OQ ANTIMETABOLITES + These drugs act in the S-phase of cell cyck - only dividing cells are responsible. FOLATE ANTAGONIST Methotrexate (Mtx) * Itisa cell cycle specific (CCS) drug and acts during $ phase of the cell cycle. [GPAT-2014] * Ithas antineopkastic, immunosuppressant and anti-inflammatory effects. * Methotrexate is the drug of choice for choriocarcinoma. It is also used in acute leukaemia's, Burkitt's lymphoma and breast cancer. Methotrexate is thought to exert its actions by Interfering with purine synthesis. [GATE-2004] Mechanism of Action Methotrexate t e Dihydrofolicacid __Dihydrofolate reductase _‘Tetrahydrofolic acid (DHFA) (DUFR) (THFA) Leucovorin Da \ Toxicity Folinic acid Synthesis of pu my and thymidylate Overcome by|—* 7) (NS-formly FH4) Citrovorum factor} DNA and RNA synthesis ‘7707680 Goat Divebeucs BEI CHEMOTHERAPY OF NEOPLASTIC DISEASE: ANTICANCE Uses of Mex inhibit CANCER ies Mne: J——+ Immunosuppressant |. Crohn's disease I——+ Abortion |» Non hodgkin lymphoma J+ Choriocarcinoma I» Ectopic pregnancy J» Rheumatoid arthritis Pemetrexed + Pemetrexed is an antifolate drug activated in the cells to its polyglutamate form which inhibits DHFR. + It is approved for use in mesothelioma and non-small cell lung cancer along with other drugs used in lung cancer. PURINE ANTAGONISTS Purine analogs a incorporated DNA synthesis olite —* into DNA = Breaks in DNA strand’ 6-Mercaptopurine (6-MP) and 6-Thioguanine (6-TG) 6-Mercaptopurine, 6-Thioguanine are converted into corresponding ribonucleotide which inhibit the conversion of Inosine monophosphate to adenine & guanine nuckotide (Inhibit protein synthesis). Pentostatin is a purine derivative antimetabolite drugs and its mechanism of action inhibit adenosine deaminase. [GATE-2005] © 6-MP ako has immunosuppressant action. Allopurinol interface with the metabolism of 6-MP by inhibiting the enzyme xanthine oxidase and increases the antineoplastic effect of 6-MP. [GATE-1998] 6-MP is used mainly in acute lymphocytic leukaemia. Bone marrow depression is the major adverse effect of 6-MP. Mechanism of Action 6-MP and 6-TG is converted intracellularly to TGMP (6-thioguanylic acid) by the enzyme Hypoxanthine guanine phosphoribosyl transferase (HGPRT) TGMP is further converted to the di and triphosphate, thioguanosine diphosphate and thioguanosine triphosphate the biosynthesis of purines and also the phosphorylation of GMP to guanosine diphosphategras Fludarabine Fludarabine, an analog of vidarabine (antiviral drug), Is converted to an active triphosphate derivative which inhibits DNA polymerase. against hairy cell leukaemia and non- Hodgkin's lymphoma. « Fludarabine is also effective PYRIMIDINE ANTAGONIST Thymine and cytosine are the to active metabolites which resemble nal 2 pyrimidines present In the DNA. Pyrimidine analog are converted tural nuckotides. Fluorouracil (5-FU) SPU is activated to fluorodeoxyuridine monophosphate (FAUMP), This interferes with DNA tion by inhibiting thymidylate synthetase enzyme. [GPAT-2023] Synthesis and funcet §-fluorouracil the anticancer effect in the $ phase of the cell cycle. breast, ovary, skin, recurrent/metastatic salivary gland * It is used in gastrointestinal tract (GIT), tumours, etc. m of Action Mechat Fluorouracil (pyrimidine analog) Active metabolite Inhibits thymidylate synthetase Incorporated into DNA and RNA Inhibits thymine synthesis Inhibits DNA and RNA synthesis Cytosine arabinoside or Cytarabine «It isthe most effective agent in acute myeloblastic leukaemia. .d into the DNA and inhibits ine arabinoside triphosphate is incorporate: The active metabolite cytosi DNA polymerase and thereby inhibits DNA synthesis. yw depression. «It causes nausea, vomiting and bone marro Gemcitabine «it isa recently developed analog of cytarabine with MOA similar to it 5 Gemcitabine is used in pancreatic, lung, cervical, bladder, ovarian and breast cancers. jcenee oe ein of diphosphate ribonucleotide —> deoxynucleotide > LNA synthesis reduce : triphosphate O MICROTUBULE DAMAGING AGENTS VINCA ALKALOIDS Vincristine and Vinblastine are vinca alkaloids obtained from the leaves of vinca rosea, the(CHEMOTHERAPY OF NEOPLASTIC DISEASE : ANTICANCER DRUGS _ EE Vinorelbine is a semisynthetic derivative. ine and Vinblastine differ only in the substitution on the N-atom of the dihydroindok © Vincri: nucleus. Vincristine and Vinblstine act by binding with the protein tubulin and arrest at metaphase. [GATE-1988] Mechanism of Action Vincristine and Binds to beta-tubulin Disruption vinblastine (drug-tubulin complex) of mitotic spindle Cell division |, Metaphase arrest <—— Chromosomes fail to ited move apart during mitosis Vincristine Vincristine (oncovin) used in the treatment of Childhood leukaemia’s, Childhood tumours - Wilm’s tumour, Neuroblastoma, Hodgkin's disease. Vinbhstine * Vinbhstine used in the treatment of Hodgkin's disease, Carcinoma breast, Testicular tumours. Vinorelbine + It isa semisynthetic vinca alkaloid used intravenously in lung cancers (non-small cell type), breast and ovarian cancers. ‘TAXANES * Taxanes are a chss of diterpene. It includes Paclitaxel and Docetaxel. * Taxanes enhance stability of microtubule, preventing the separation of chromosomes during anaphase. Paclitaxel * Paclitaxel is a Taxane derived from the bark of the Western yew tree. + Itis ako found to be effective in the cancers of ovary, head and neck, breast, oesophagus anc lungs ‘> Mechanism of Action Paclitaxel Binds to B -tubulin————> Enhances Polymerization Death of thecell_|<—— Inhibits mitosis. <—— Formation of abnormal [GATE-2003]} microtubules Docetaxel and Cabazitaxel * They are similar in actions, toxicity and uses to paclitaxel. * Cabazitaxel is useful in resistant prostatic cancers. ‘BarveEEE EEE GPAT DISCUSSION CENTER ‘Makes Study Exsy 2 TOPOISOMERASE-11 INHIBITORS/ EPIPODOPHYLLOTOXINS Etoposide , i erivatil dophyllotoxin, a plant glycoside. It is a semisynthetic derivative of podophy! span Bs pn compe Epipodophyllotoxin inhibit topoisomerase II by stal prevent the unwinding of DNA. Itis not a mitotic inhibitor, but arrests cells in the G, phase. ; te * Etoposide is used in testicular tumours, lung cancer in combination with o ‘+ _Side effects are - Bone marrow suppression, GI side effect. DNAstrand___ [Deathof thecell her cytotoxic druy Binds to DNA & topoisomerase II —> (Etoposide-DNA-Topoisomerase—> preakages complex) II OQ TOPOISOMERASE-I INHIBITORS/ CAMPTOTHECIN ANALOGUS ca acuminata. [GATE-2009] * Camptothecin are obtained from the Chinese tree Camptothes * They damage DNA during replication; act in the $ phase and arrest cell cyck at G, phase. * Two semisynthetic derivatives are - Topotecan & Irinotecan. Act by inhibiting topoisomerase I (this enzyme nicks, negative supercoil and reseal DNA Strar Common side effect are bone marrow suppression and GI disturbance. Etoposide Topotecan ‘* Itis used in metastatic carcinoma of ovary and small cell lung cancer after primary chemother has failed Combined with cisplatin, it has been used in cervical cancer. Irinotecan © It produces the cholinergic effects because it inhibits the acetylcholinesterase. Q antiBroTics Obtained from microorganisms and have prominent antitumour activity. Practically all intercalate between DNA strand and interfere with its template function. Actinomycin D (Dactinomycin) Obtained from streptomycer parvulus. Highly efficacious in Wilm’s tumour & rhabdomyosarcoma (Cancer of Skeletal musck). jis and also causes breaks in the DNA. It inhibits DNA-dependent RNA synthe: It is also used in Kaposi's sarcoma and Ewing's tumour. Dactinomycin is also an immunosuppressant and is used in renal transplants. Doxorubicin and Daunorubicin © They are anthracyclines. © They form a compkx with topoisomerase II and inhibit it (GATE-2006}. * They act on the ‘S’ phase of the cell cycle. * Doxorubicin is isolated from Streptomyces peucetius var. caesius. [GATE-2006] Mitoxantrone © Analog of doxorubicin. Do not Produce quinone type free radicals. (9 97707686a st MOTHERAPY OF NEOPLASTIC DISEASE : ANTICANCER DRUGS non” Bleomycin «A mixture of glycopeptide antibiotics. «Inhibition of DNA synthesis. [GPAT-2023] © Bkomycin has been shown to cause cell cycle arrest in G, phase and in mitosis. + Bkomycin can also cross the blood brain barrier as it is used to treat cancers in the bra It is used in squamous cell carcinoma of the skin, carcinoma of oral cavity, head and neck cancer also used in the treatment of melanoma, Sarcoma, testicular cancer. «Its main side effects are hyperpigmentation of skin and pulmonary fibrosis. There is very little bone marrow suppression (spares bone marrow). [GPAT-2013] Mitomycin C Mitomycin C is an antibiotic isolated from Streptomyces caespitosus. [GPAT-2020] «Mitomycin metabolic activation to produce a DNA alkylating agent. « Itis mainly used in the treatment of GI tumours, cervix and bladder cancer. * Side effects are bone marrow suppression, gastrointestinal and nephrotoxicity. Q MISCELLANEOUS Hydroxyurea + Itisan analogue of urea and acts by inhibiting the enzyme ribonucleotide reductase and thereby inhibits DNA synthesis. SCAN ME « Hydroxyurea is a first-line drug for sickle cell disease in adults. ‘Tyeyet * Itacts on the ‘S’ phase of the cell cycle * It is effective orally. It has near 100% oral bioavailability. [GPAT-2023] Sas, * Adverse effects are myelosuppression and skin pigmentation. aes Ribonucleotide Hydroxyurea —| Ribonucleotide Diphosphate Reductase Deoxyribonucleotide | DNA Synthesis L-asparaginase (L-ASPase) + L-asparaginase is obtained from E. coli and is administered parenterally. [GATE-2008] L-Asparaginase Asparagine, —————————>_Asparticacid * Asparagine is amino acid required for protein synthesis. (Essential for leukaemia cell) * Itis used in acute leukaemia’s. [GATE-2008] ity - Hypersensitivity, Hyperglycaemia, Haemorrhage, Pancreatitis. T@ seoraTaa4, @ 9770768680 eapp)qe TARGETED DRUGS Tmatinib a segment of BER-ABL tyrosine kinase non-functional ste 12] pentyl ts preseribed for the treaunient of Philadelphia chromosome positive patient with Chronic myeloid eukaemia. (GPAT2010] seer ieako used in gastrointestinal tumors that express tyrosine Kinase, Gefitinib and ErlotinIb It inhibits epidermal growth factor receptor (EGFR) tyrosine .xpressed in several malignancies. domain that fixes it in a closed or = Imatinib bind jase. 2 EGER is ov Cetuximab This inhibitor of EGF receptor is a chimeric monoclonal antibody directed to the extracellular domain of the EGF receptor. Sunitinib and Sorafinib «They are tyrosine kinase inhibitors. ma and hepatocellular carcinoma and some GI «They inhibit VEGF and are used in renal cell carcino tumours. Bortezomib «It binds with high affinity to 26S proteosome and inhibits it © Bortezomib is used in refractory multiple myeloma. = Bosutinib: Another tyrosine kinase inhibitor is useful in CML resistant to other drugs. Trastuzumab «It isa humanized monoclonal antibody which binds to the extracellular domain of another subtype of EGFR termed HER2 (human epidermal growth factor receptor 2) and inhibits signal transduction. [GPAT-2023] I HORMONAL DRUGS J fy the growth of hormones dependent tumours. > They are not cytotoxic but modi + All hormones are only palliative (relieving the symptoms of disease without affecting cure). Glucocorticoids Have marked lympholytic action. Primarily used in acute childhood leukaemia and lymphomas. Apart from this effect, glucocorticoids: Y Have anti-inflammatory effect, decrease oedema associated with the tumour. Y Produce feeling of well-being. V Suppress hypersensitivity reaction due to certain anticancer drugs. estrogens «Highly effective in Prostate carcinoma. ‘Tamoxifen [GATE-2002] hly effective in breast carqerar” CHEMOTHERAPY OF NEOPLASTIC DISEASE: ANTICANCER DRUGS Progestins The progestins are useful in endometrial carcinoma. Antiandrogens « Flutamide and Finesteroid: Useful for palliative treatment of advanced carcinoma of prostate. 5-a reductase inhibitor Finasteride and dutasteride inhibit conversion of testosterone to dihydro-testosterone in prostate (and other tissues), have palliative effect in advanced carcinoma prostate; occasionally used Aromatase inhibitors * Used in hormone-dependent breast cancer in postmenopausal women. GnRH agonists * Continuous administration, suppresses the pituitary gonadotropins by downregulating GnRH receptors. «These agents produce palliative effects in advanced prostatic and breast cancers. Thalidomide + Banned in 1961 for its teratogenic effect, but reintroduced as immunomodulator, and angiogenesis inhibitor antitumour drug. + Has anxiolytic, antiemetic, adjuvant analgesic/antipyretic properties and has been found to counteract cancer associated cachexia and retard tumour growth by inhibiting angiogenesis. «It probably acts by suppressing TNFa and by modulating IL-2. DRUG OF CHOICE neem Temozolomide Brain tumour, Glioblastoma Cyclophospha: Lung cancer Melphalan Ovarian and Testicular carcinoma, Multiple myeloma Cytarabine + Idarubicin/ Daunorubicin Acute myeloid leukaemia Bleomycin + Cisplatin + Etoposide Cancer testis Doxorubicin + Bleomycin + Vinblastine+ Hodgkin's disease stage I, II stage Ill and Dacarbazine WV Busulfan Myeloid leukaemia Surgery + Radiotherapy followed by Wilm’s tumour Vincristine + actinomycin Chlorambucil Chronic myeloid leukaemia Tamoxifen Highly effective in breast carcinoma Estrogen Highly effective in Prostate carcinoma 5-Fluoro uracil + Leucovorin + Oxaliplatin | Colon cancer Gemcitabine Pancreatic carcinoma Cyclophosphamide + Non-Hodgkin's lymphoma Hydroxydaunorubicin + Oncovin + Prednisolone + Rituximab Goat Discussion Center Pr. Lid. | ©) www.gdeonlneestio, ww Dowaload “GDC CLASSES" App (Type <4gpacom | J gucgpatOOT@gmallcom | © 8601227444, @ 9T7OT6SE50 IDC CLASSES in Paystore to Dowaloadtheapp)