1. ANTINEOPLASTIC DRUGS - MOLECULAR TARGETED AGENTS WEEK-9 MR160 Chapter 29 (p.187-199) Chapter 31 (p.211-217)

2. Terminology Neoplasms – abnormal, uncontrolled growths that cause cancer Malignancies – neoplasms capable of causing death of the entire organism Carcinoma – a malignancy of epithelial cells (80% of all malignancies) Anti-neoplastic drugs – often used after surgery to treat microscopic ‘remnants’

3. Alkylating agents Attach “alkyl groups” (organic side-chains) to the cancer cell’s DNA This interferes with the cancerous cells’ function Examples: Cytoxan: (cyclphosphamide); Leukeran (chlorambucil); Mustargen (mechlorethamine)

4. Anti-Metabolites Compete with, replace, or antagonize a metabolic process in the body These work because neoplastic cells grow more rapidly than normal cells, so in theory the fast-growing (abnormal) cells will be affected to a much greater degree Unfortunately, this is not always the case Examples: Cytosar (cytarbine);DTIC (dacarbazine); Gemzar (gemcitabine); 5-FU

5. Hormones Certain tumors are hindered by altering hormone levels Reproductive-tract (sex organs) Examples: Coticosteroids; Sex hormones: antiandrogens: Eulexin (flutamide); estrogens: Megace (megestrol); Antiestrogens: Nolvadex (tamoxifen); Inhibitors of Pituitary Hormones: Zoladex (goserelin)

6. Anti-Tumor antibiotics Interfere with DNA or RNA synthesis Examples: bleomycin; dactinomycin; daunorubicin; doxorubicin (Adriamycin); mitomycin-C

7. Enzyme inhibitors Interrupt or interfere with certain tumor enzymes that are needed for its growth Examples: Elspar (asparaginase); etoposide; Gleevec (imatinib)

8. Immuno-modulating agents Enhance or augment the human body’s own defenses, allowing it to more effectively attack cancerous cells Examples: Proleukin (aldesleukin); Interferon alfa;

9. Molecular medicine & Gene therapy These treat cancer at the cellular level Tend to be much more ‘specific’ … (more on these in chapter-31)

10. Platinum analogs The platinum component binds to the DNA and proteins of the cancer cell, disrupting their function Examples: carboplatin; cisplatin;

11. Miscellaneous Drugs These ‘other’ agents don’t really fit into any of the previous categories Work by various mechanisms-of-action (MOA) ……… see Table 29-1 on page-196 ……… Examples: Taxol (paclitaxel); Taxotere (docetaxel); Hydrea; vinblastine; vincristine; Supportive: darbopoetin – epoetin: filgrastim (neupogen)

12. Review questions … A ‘neoplasm’ is caused by? a)Carcinoma b)Uncontrolled cell-division c)Rapidly dividing healthy tissues

13. Answer is … b) uncontrolled cell division --- keyword of course is ‘uncontrolled’!

14. Review question #2 The ‘anti-metabolites’ work by … a)Interfering with abnormal cell growth b)Alkylating the ‘offending’ cells c)Interfering with some phase of normal cellular metabolism d)Interfering with abnormal metabolic processes

15. Answer to #2 … c) antimetabolites interfere with some phase of normal cellular metabolism

16. MOLECULAR & TARGETED THERAPIES … a brief discussion (detail in textbook) Gene therapy – “the application of genetic- principles in treating human disease” Stem cells ‘Targeted’ – directed at abnormal/missing site Monoclonal antibodies *Immune system suppressors (RA, Crohn’s) *Cancer agents

17. STEM CELLS Potential to develop into any tissue May manufacture a missing substance, or create new tissue-cells to replace the damaged ones Research continues!

18. TARGETED therapy Rapidly developing area of Pharmacology Cancer chemotherapy (leukemia, certain breast cancers, renal cell cancer) Auto-Immune disorders (MS, rheumatoid- arthritis, Crohn’s disease, thyroiditis) Psoriasis tx – targets certain ‘lymphocytes’ that produce the protein cytokine, a regulator of immune-responses

19. MONOCLONAL antibodies review pages 212 – 215 carefully Used in several ways therapeutically … 1) to suppress the immune-system (prevent the rejection on transplanted organs, as disease modifiers in diseases like RA or Crohn’s disease) 2) various types of cancer 3) psoriasis

20. THANKS! …