Oncology

Medical Pharmacology Chapter 33-34: Anticancer Drugs

Natural Products:

Topoisomerase Inhibitors: Camptothecins

**"Molecular target identificaiton for translation medicine: the anticancer topoisomerase I inhibitors."**¹¹

Attribution: Pommier Y Molecular target identification for translation medicine: the anticancer topoisomerase I inhibitors https://www.youtube.com/watch?v=PYYB9_gMp_E&list=PLCDBD87003961708F (5/2011) JHU Center for Biotechnology Education- 6th Annual Symposium JHU Advanced Academic Programs Youtube Channel: https://www.youtube.com/channel/UCL_uzkLMTCSpEZ54leYViYg

Camptothecins: Irinotecan and topotecan:

Camptothecin is classified as an alkaloid that was identified in plant extracts from Camptotheca acuminata , while searching for antineoplastic agents.

***Camptotheca acuminata***

Camptotheca acuminata (Happy tree / Tree of Life) Ons zaden https://www.onsseeds.com/camptotheca_acuminata

**Camptothecin**⁹

Attribution: Fvasconcellos (talk · contribs) [Public domain] https://commons.wikimedia.org/wiki/File:Camptothecin.svg

**Binding of Camptothecin to DNA and topoisomerase Icc**¹⁰

Attribution: Yikrazuul Wikipedia: Camptothecin binding to DNA (above blueline) and to topoisomerase (redline) https://en.wikipedia.org/wiki/Camptothecin

There are two derivatives of camptothecin approved by the FDA for use in treating various cancers.
These agents are irinotecan (Campto) and topotecan (Hycamtin).
- Review:
  - The enzyme DNA topoisomerases function to promote relaxation supercoil DNA torsional stress by enhancing catalysis.
  - The consequence of this action is sufficient to allow replication, repair as well as transcription.
    - We are now considering the first of two classes of topoisomerase (I and II).
      - These topoisomerases promote DNA strand breakage and resealing.
        
        Camptothecin analogs limit topoisomerase I function (inhibition of the enzyme aciton).
        
        Examples of drugs that inhibit topoisomerase II include the anthracycline class, epipodophyllotoxins and acridines.

References
Wellstein A Giaccone G Atkins MB Sausville Chapter 66: Cytotoxic Drugs in Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e, Brunton LL Hilal-Dandan R Knollmann BC, eds) 2018. Sausville EA Longo DL Chapter 103e Principles of Cancer Treatment, in Harrison's Online (Dennis L. Kasper, Anthony S. Fauci, Stephen L. Hauser, Dan L. Longo, J. Larry Jameson, Joseph Loscalzo, Eds.), Harrison's Principles of Internal Medicine, 19th edition, The McGraw-Hill Companies, Inc. 2015. Chu E Cancer Chemotherapy Chapter 54 in Basic & Clinical Pharmacology, 14 e (Katzung BG The McGraw-Hill Companies, 2018 (on-line edition) Tew KD Chapter 17: Alkylating Agents in Principles & Practice of Oncology (DeVita, JR VT Lawrence TS Rosenberg SA, eds) 10e Wolters Kluwer Health 2015. Collins JM Cancer Pharmacology Chapter 29 in Abeloff's Clinical Oncology (Niederhuber JE Armitage JO Doroshow JH Kastan MB Tepper JE, eds) 5e Elsevier Churchill Livingstone, Philadelphia, PA 2014. Wellstein A Giaccone G Atkins MB Sausville Chapter 67: Pathway-Targeted Therapies: Monoclonal Antibodies, Protein Kinase Inhibitors, and Various Small Molecules in Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 13e, Brunton LL Hilal-Dandan R Knollmann BC, eds) 2018. Thomas A Do K Kummar S Doroshow JH Pommier Y Chapter 23: Topoisomerase-Interacting Agents in DeVita, JR VT Lawrence TS Rosenberg SA, eds) 11e Wolters Kluwer Health 2018. Thomas A Pommier Y Chapter 14 Topoisomerase Inhibitors in: Cancer Chemotherapy, Immunotherapy and Biotherapy Principles and Practice Chabner BA Longo DL, eds 6e Wolters Kluwer 2019. Camptothecin: Wikipedia https://commons.wikimedia.org/wiki/File:Camptothecin.svg; attritubution Fvasconcellos (talk · contribs) [Public domain] Camptothecin-topoisomerase-DNA binding: Wikipedia https://commons.wikimedia.org/wiki/File:Camptothecin_binding.svg Attribution: Yikrazuul [Public domain] Pommier Y Molecular target identificaiton for translation medicine: the anticancer topoisomerase I inhibitors. The Johns Hopkins University Center for Biotechnology Educitons: 6th Annual Symposium. Published May 20, 2011 https://www.youtube.com/watch?v=PYYB9_gMp_E&list=PLCDBD87003961708F
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