1. Good afternoon..... Good afternoon....

2. GROWTH FACTORS AND CELL SIGNALLING IN THE PATHOGENESIS OF CANCER ---Dr ANINDYA MUKHERJEE PGT,dept of radiation oncology

3. MOLECULAR BASIS OF CANCER

5. Essential alterations for malignant transformation

7. Few oncogenes,overview.....

11. Domains of EGFR undergoing mutation...

12. MECHANISM 3…. Mutation and rearrangements:- a) FLT3 (coding FMS like tyrosine kinase 3) amplified in myeloid leukaemias b) PDGF receptor point mutation results in gliomas, leukaemias c) cKIT (with tyrosine kinase activity) mutation results in GIST,leukaemias.

14. C2) Less commonly due to point mutations... viz,JAK2 point mutation results in Polycythemia vera

15. C3) Alterations in nonreceptor tyrosine kinase Mostly due to translocations..

21. CELL CYCLE ARREST AT G1-S CHECKPOINT AND S PHASE DELAY,contd....

22. G2-M CHECKPOINT : Monitors the completion of DNA replication and checks whether the cell can safely initiate mitosis and separate sister chromatids. Arrest of cell cycle at this checkpoint involves both p53 -dependent and p53-independent mechanisms. Defects in G1-S and G2-M transition checkpoints are a major cause of genetic instability in cancer cells.

23. CELL CYCLE ARREST AT G2-M CHECKPOINT...contd..

25. CELL CYCLE EFFECTS OF ANTICANCER DRUGS PHASE CCS DRUGS CCNS DRUGS G1-S ETOPOSIDE PLATINUM COMPOUNDS S ANTIMETABOLITES ALKYLATING AGENTS G2-M BLEOMYCIN,ETOPSIDE ANTHRACYCLINES,DACTI NOMYCIN M VINCA ALKALOIDS,TAXANES,IXA BEPILONE,ESTRAMUSTIN E MITOMYCIN,CAMPTOTHE CINS

26. MONOCLONAL ANTIBODIES... FEW EXAMPLES AND INDICATIONS MONOCLONAL ANTIBODY TARGET INDICATION Rituximab,Ibritumonab CD 20 B cell NHL Gemtuzumab,Ozogamicin CD 33 CD 33 positive AML Ocrelizumab,oftamumab CD 20 SLE Alemtuzumab CD 52 B cell CLL Adalimumab,Infliximab TNF-alpha Rheumatoid arthritis Trastuzumab Her2-neu Breast cancer Donesumab RANK ligand Osteoporosis Bevazicumab VEGF Colorectal cancer Ranibizumab VEGF Neovascular macular degeneration Cetuximab EGFR Head neck CA.colorectal CA Panitimumab EGFR Colorectal carcinoma

28. Sites of action on EGFR receptor-an example of targeted therapy...

30. HORMONES AND RELATED AGENTS : CLASS DRUGS USED IN SIDE EFFECTS Glucocorticoids Prednisolone Combination Chemotherapy in leukaemia,lymphoma Fluid retentn,HTn,diabetes,obesity,infections,etc Estrogens Estrogen Prostrate cancer Antiandrogenic effects Progestins MDPA,Megestrol 2 nd line therapy for metastatic hormone dependent breast and endometrial cancer Fluid retention,bloating,oedema Antiandrogens Flutamide,bicalutamide Prostatic cancer Hepatic dysfunction,gynaecomastia,hot flushes GnRH agonists Goserelin,Nafarelin,Leuprolide Advanced prostratic cancer Transient flare up,hot flush,gynaecomastia,osteoporosis. GnRH antagonists Cetorelix,Ganirelix,Abarelix Advanced prostratic cancer Same as that of agonists except no flare-up occurs

31. HORMONAL AGENTS Contd.... CLASS DRUGS USED IN SIDE EFFECTS SERMs(Selective estrogen receptor modulators) Tamoxifen,tormifene Early and metastatic breast carcinoma Menopausal symptoms,thromboembolism,endometrial cancer,etc Pure ER antagonist (Selective estogen receptor down regulators-SERDRs) Fulvestrant Metastatic breast cancer limited Aromatase inhibitors (inhibits conversion of androstendione to estrone) First gen -aminoglutethimide Second gen -Formestane,fadrozole,rogletimide Third gen -exemestane,anastrozole,letrozole,vorozole Advanced breast carcinoma Adrenal suppression and myleosuppression due to aminoglutethimide, others may cause hot flushes,arthralgias and fatigue

32. Thank you....