BEGIN:VCALENDAR PRODID:-//eluceo/ical//2.0/EN VERSION:2.0 CALSCALE:GREGORIAN BEGIN:VEVENT UID:2adfdc886df82763d5ac101ae639feda DTSTAMP:20260706T091422Z SUMMARY:Discovering targeted cancer drugs and chemical probes DESCRIPTION:Join us for the first instalment of the 2021 Almroth Wright lec ture series with Professor Paul Workman FRS.\nPlease register in advance i f you would like to attend. This event will be hosted via Microsoft Teams\ ; once you have registered\, you will receive a calendar invitation and li nk via email.\nFor more information about the Almroth Wright lecture serie s\, please visit our website.\nAbstract\nOne in two people will develop ca ncer in their lifetime. The UK’s cancer survival has doubled over the la st four decades such that around half of patients now survive over ten yea rs. However\, outcomes for cancers such as lung\, liver\, brain and pancre as remain very poor. The discovery and development of personalised medicin es have been underpinned by our enhanced mechanistic understanding of canc er biology and genetics\, accelerated by genome sequencing. However\, a ma jor challenge to drug treatment is the extensive cellular and genetic hete rogeneity of tumours and the ability of cancer cells to adapt\, evolve and become resistant. I will briefly cover this background before describing examples of our recent research to discover new molecularly targeted drugs . I will also interweave examples of my other major personal research inte rest\, which is the discovery of high-quality small-molecule chemical prob es to investigate the role of specific proteins in fundamental biology and disease pathology.\nFollowing our discovery of Heat Shock Protein 90 mole cular chaperone inhibitors and progression of luminespib to the clinic (wi th Vernalis and Novartis)\, we switched our attention to discover inhibito rs of the transcription factor Heat Shock Factor 1 or HSF1. HSF1 plays an important role in oncogenesis and the maintenance of the cancer state. HSF 1 is itself hard to drug directly and so we adopted an approach based on p henotypic screening. I will describe our more than ten-year journey from t he initial screen to the discovery of a chemical probe and then a clinical candidate HSF1 pathway inhibitor that shows particular potential for the treatment of ovarian clear cell carcinoma and multiple myeloma.\nIn collab orative studies\, we have progressed to a first-in-child clinical trial ev aluation of the dual-selective cyclin-dependent kinase (CDK) 9/2 inhibitor fadraciclib (CYC065). This drug was discovered by our team at ICR in coll aboration with Cyclacel. We then discovered its therapeutic potential in m odels of aggressive paediatric neuroblastoma that is driven by another tra nscription factor\, MYCN. Like HSF1\, MYCN is also hard to drug directly\, but its expression is decreased by fadraciclib’s inhibition of the tran scriptional kinase CDK9. The additional inhibition of CDK2 by fadraciclib induces apoptotic cell death in MYCN neuroblastoma cells and produces prol onged tumour response and survival in mouse models.\nAbout the speaker\nPa ul Workman is Chief Executive and President of The Institute of Cancer Res earch (ICR)\, London\, and Harrap Professor of Pharmacology and Therapeuti cs at the ICR. He was the Founding Director of the ICR/Imperial Cancer Cen tre of Excellence and the ICR/Imperial CRUK Convergence Science Centre. Pa ul is a Fellow of the Royal Society\, Academy of Medical Sciences\, Royal Society of Chemistry\, Royal Society of Biology and the European Academy o f Cancer Sciences. He is also a Cancer Research UK (CRUK) Life Fellow.\nTr ained in biochemistry and cancer pharmacology\, Paul is a leader in the di scovery of molecularly targeted cancer drugs for personalised treatment an d the identification of small-molecule chemical probes to investigate prot ein function in fundamental biology and disease pathology. At AstraZeneca\ , he led the biology of the team that discovered gefitinib (Iressa)\, appr oved in EGFR mutant lung cancer. As Director of ICR’s CRUK Cancer Therap eutics Unit\, Paul oversaw the discovery of 20 drug candidates\, eleven of which have progressed into the clinic. Paul is especially renowned for hi s innovative personal research in the discovery\, chemical biology\, and m olecular pharmacology of drugs acting on protein kinases\, PI3 kinases and the molecular chaperone HSP90\, and he is the originator of the widely us ed Pharmacologic Audit Trail framework for biomarker-led drug development. He was a scientific founder of Piramed Pharma (acquired by Roche) and Chr oma Therapeutics and is Executive Director of the non-profit Chemical Prob es Portal.\nPaul has published more than 500 scientific articles\, receivi ng over 45\,000 citations. He has received numerous personal honours and a wards. He led the ICR/Royal Marsden team that won the 2012 American Associ ation of Cancer Research Team Science Award\, and under his leadership\, t he ICR was awarded a 2017 Queens’ Anniversary Prize for its outstanding track record in cancer drug discovery. Paul writes\, lectures and blogs ab out cancer research and drug discovery. URL:https://www.imperial.ac.uk/events/133287/discovering-targeted-cancer-dr ugs-and-chemical-probes/ DTSTART;TZID=Europe/London:20210504T170000 DTEND;TZID=Europe/London:20210504T180000 LOCATION:United Kingdom END:VEVENT BEGIN:VTIMEZONE TZID:Europe/London BEGIN:DAYLIGHT DTSTART:20210504T170000 TZNAME:BST TZOFFSETTO:+0100 TZOFFSETFROM:+0100 END:DAYLIGHT END:VTIMEZONE END:VCALENDAR