Paul Andrews (scientist)

Paul L. R. Andrews (born 1953, Worcester, England) is a British physiologist whose basic research on the mechanisms of action and efficacy of antiemetic substances contributed to development of treatments for anti-cancer chemotherapy-induced nausea and vomiting.[1][2]

Paul L. R. Andrews
Born
Worcester, England
NationalityUnited Kingdom
Alma materUniversity of Sheffield
OccupationScientist
Organizations
AwardsPfizer Academic Award

He also conducted research on the comparative neurophysiology of fish and octopus, partly undertaken in collaboration with J. Z. Young.[3]

He received the Pfizer Academic Award in 1989 for "studies which have furthered our understanding of the nervous control of gut function".

Career

Andrews was educated at the University of Sheffield where he obtained a B.Sc degree in physiology in 1974 followed by a Ph.D in neurophysiology in 1979 before becoming Lecturer in physiology at the University of Edinburgh in 1980. He was appointed Lecturer in the Department of Physiology at St. George's Hospital Medical School (now known as St George’s, University of London) in 1983, becoming a professor there in 1998.

He is an emeritus professor in the Division of Biomedical Sciences at St George’s, University of London and senior research fellow at the Stazione Zoologica Anton Dohrn, Naples, Italy.

Research work

Paul Andrews studied the neurophysiological and pharmacological mechanisms and efficacies of receptor antagonists[4][5] that have contributed to the development of treatments for reducing the effects of nausea and vomiting (emesis) associated with treating cancer by cytotoxic drugs (e.g. cisplatin).

He contributed to demonstrating the anti-emetic efficacy of tachykinin NK1 receptor antagonists[5] currently in widespread use (see Clinical use) for the treatment of chemotherapy-induced nausea and vomiting. Collaborating with Gareth Sanger, who demonstrated the anti-emetic efficacy of 5-hydroxytryptamine3 (5-HT3) receptor antagonists,[6] they proposed that 5-HT3 receptor antagonists work to prevent cytotoxic-associated vomiting by blocking the ability of 5-HT to activate 5-HT3 receptors on abdominal vagal nerve terminals. They proposed this desensitizes the vagus to the pro-emetic stimulatory actions of 5-HT and other substances (e.g., prostanoid) released during the cytotoxic treatment.[1]

Clinical use

The selective 5-HT3 receptor antagonist BRL43694 or granisetron was developed by Beecham Pharmaceuticals following the experiments showing its anti-emetic potential.[7] Granisetron is available as a generic and is produced by Roche Laboratories under the trade name Kytril.

Four NK1 receptor antagonists have been approved for human clinical use including aprepitant which is sold under the brand name Emend.

Clinical reviews indicate selective 5-HT3 receptor antagonists are an essential component of anti-emetic therapy in patients undergoing chemotherapy and together with the NK1 receptor antagonists are important additions to the treatment of cancer and have helped to reduce health care costs.[8][9]

The Multinational Association for the Support of Cancer Care guidelines[10] for high emetic-risk chemotherapy recommends use of an NK1 receptor antagonist in combination with a 5-HT3 receptor antagonist and dexamethasone, a corticosteroid medication, for optimal efficacy.[11]

References
  1. Sanger, G.J., Andrews, P.L.R. (2018) "A history of drug discovery for treatment of nausea and vomiting and the implications for future research". Frontiers in Pharmacology 9, 913. doi: 10.3389/fphar.2018.00913
  2. Daphne Christie; Tilli Tansey, eds. (2007) "The Discovery, Use and Impact of Platinum Salts as Chemotherapy Agents for Cancer", Wellcome Witnesses to Contemporary Medicine, History of Modern Biomedicine Research Group, ISBN 978-0-85484-112-7.
  3. P. L. R. Andrews & J. Z. Young (1993)“Gastric motility patterns for digestion and vomiting evoked by sympathetic nerve stimulation and 5-hydroxytryptamine in the dogfish Scyliorhinus canicula” Philosophical Transactions of the Royal Society B 342.
  4. Andrews, P. L. R., Rapeport, W. G., and Sanger, G. J. (1988) "Neuropharmacology of emesis induced by anti-cancer therapy" Trends in Pharmacological Sciences 9, 334–341. doi: 10.1016/0165-6147(88)90106-X
  5. Watson, J.W., Gonsalves, S.F., Fossa, A.A., McLean, S., Seeger, T., Obach, S., Andrews, P. L. R. (1995) "The anti-emetic effects of CP-99, 994 in the ferret and the dog: role of the NK1 receptor" British Journal of Pharmacology 115 84–94.
  6. Miner, W.D. and Sanger, G.J. (1986) "Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism" British Journal of Pharmacology 88 497–499.
  7. Bermudez, J., Boyle, E. A., Miner,W. D., and Sanger, G. J. (1988). "The anti-emetic potential of the 5-hydroxytryptamine3 receptor antagonist BRL 43694". British Journal of Cancer 58, 644–650.
  8. Currow, D. C., Coughlan, M., Fardell, B., and Cooney, N. J. (1997). [https://www.jpsmjournal.com/article/S0885-3924(97)00079-1/pdf "Use of ondansetron in palliative medicine"] Journal of Pain and Symptom Management 13, 302–307.
  9. Warr, D., and DeAngelis, C. (2009). "Controlling nausea and vomiting in patients undergoing chemotherapy. Toward more effective clinical practice" Oncology Exchange 8, 23–27.
  10. Multinational Association for the Support of Cancer Care (MASCC). "MASCC/ESMO Antiemetic Guidelines".
  11. Herrstedt, J., Roila, F.,Warr, D., Celio, L., Navari, R.M., Hesketh, P.J., Chan, A., Aapro, M.S. (2017). "Updated MASCC/ESMO consensus recommendations: prevention of nausea and vomiting following high emetic risk chemotherapy" Support Care Cancer 25, 277–288.
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