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Title Cancer Drug Discovery
Course number 5215
Programme Tumörbiologi och onkologi (FoTO)
Language English
Credits 1.5
Date 2020-09-07 -- 2020-09-11
Responsible KI department Institutionen för medicinsk biokemi och biofysik
Specific entry requirements Students must have acquired basic knowledge (BSc level) in cell biology, systems biology or chemistry.
Purpose of the course This course describes the steps, processes and approaches needed for drug discovery with a focus on oncology. Through lectures and interactive workshops, the students will learn about current drug discovery techniques, from screening for hit discovery to the synthesis of the final drug candidate through lead optimization. Aspects of clinical testing and precision medicine will also be addressed.

In this 5 day course, students will attend lectures by prominent scientists from academic and industry active in the fields of drug screening, drug library design and logistics, disease models, drug development, medicinal chemistry, image analysis, chemoinformatics, precision medicine, and clinical trials. The students will also participate in a group-based learning project to design their own screening strategy, and site-visits to drug discovery companies based in Stockholm, as well as the screening platform at SciLifeLab Chemical Biology Consortium Sweden.

At the end of the course, the students should have a good overview and understanding of the drug discovery workflow in cancer research, allowing them to pinpoint potential career directions for their own scientific paths.
Intended learning outcomes At the end of the course the student is expected to be able to:

Knowledge and understanding:
-Describe, define and understand the different drug discovery approaches used in both academia and industry.
-Familiarity with the drug discovery process through to a clinical implementation.

Competence and skills
-Ability to describe the concepts and terminology of drug discovery in cancer.
-Understanding the different screening strategies and the associated benefits and shortcomings.
-Ability to describe and understand how a compound can become a drug and its clinical implications.

Judgement and approach
-Demonstrate the ability to understand the concepts of drug discovery both written and orally in the workshop.
-Evaluate how a drug discovery campaign can be used to discover new anti-cancer drugs.
-Evaluate how drug discovery techniques can be currently used in a clinical setting for precision medicine.
Contents of the course The main blocks of the course include:

Drug discovery in pharma and academia: a perspective
-Chemoinformatics
-Drug Library design
-Model systems

Drug discovery strategies:
-Target-based in vitro screens
-Cell-based phenotypic screens
-Virtual screens
-High-throughput phenotypic screening
-High content imaging
-Image analysis
-Multi-parametric analysis

Target identification:
-Thermal Shift (CETSA and others)
-CRISPR
-Transcriptomics (cMap)
-PISA

Lead optimization and Medicinal chemistry
-Journey from compound to drug
-ADME and toxicity

Clinical trials and patient stratification
-Diagnostics
-Drug repurposing in personalised cancer medicine

Workshop: design your screening strategy to target one of the hallmarks of cancer
Teaching and learning activities -Lectures
-Workshops
-Site-visits
Compulsory elements Attendance to all lectures and workshops are compulsory.
Examination The examinations will consist of a written report of max. 2 pages, and a short oral presentation of a mock drug discovery project.

The project should be well motivated in background of the current state of knowledge, or lack thereof, in the cancer research area of choice, or the student's own scientific path.

Each student should ask questions or comment on the other student's presentations at the final session of the course.

One needs to show that all intended learning outcomes are reached for a pass.
Literature and other teaching material Required Reading:

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–674. doi:10.1016/j.cell.2011.02.013 (https://www.ncbi.nlm.nih.gov/pubmed/21376230)

Swinney DC, Anthony J. How were new medicines discovered?. Nat Rev Drug Discov. 2011;10(7):507–519. Published 2011 Jun 24. doi:10.1038/nrd3480 (https://www.nature.com/articles/nrd3480)

Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol. 2011;162(6):1239–1249. doi:10.1111/j.1476-5381.2010.01127.x (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058157/)

Recommended Literature:

Arrowsmith CH, Audia JE, Austin C, et al. The promise and peril of chemical probes. Nat Chem Biol. 2015;11(8):536–541. doi:10.1038/nchembio.1867 (https://www.nature.com/articles/nchembio.1867)

Blagg J, Workman P. Choose and Use Your Chemical Probe Wisely to Explore Cancer Biology . Cancer Cell. 2017;32(1):9–25. doi:10.1016/j.ccell.2017.06.005 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5511331/)

Boutros M, Heigwer F, Laufer C. Microscopy-Based High-Content Screening. Cell. 2015;163(6):1314–1325. doi:10.1016/j.cell.2015.11.007 (https://www.cell.com/cell/fulltext/S0092-8674(15)01487-7?rss=yes)

Jones LH, Bunnage ME. Applications of chemogenomic library screening in drug discovery. Nat Rev Drug Discov. 2017;16(4):285–296. doi:10.1038/nrd.2016.244 (https://www.nature.com/articles/nrd.2016.244)

Feng Y, Mitchison TJ, Bender A, Young DW, Tallarico JA. Multi-parameter phenotypic profiling: using cellular effects to characterize small-molecule compounds. Nat Rev Drug Discov. 2009;8(7):567–578. doi:10.1038/nrd2876 (https://www.nature.com/articles/nrd2876)

Horvath P, Aulner N, Bickle M, et al. Screening out irrelevant cell-based models of disease. Nat Rev Drug Discov. 2016;15(11):751–769. doi:10.1038/nrd.2016.175 (https://www.nature.com/articles/nrd.2016.175)
Number of students 8 - 20
Selection of students Selection will be based on 1) the relevance of the course syllabus for the applicant's doctoral project (according to written motivation), 2) start date of doctoral studies (priority given to earlier start date)
More information -List of speakers/lecturers:
Brinton Seashore-Ludlow (KI)
Jordi Carreras-Puigvert (KI)
Päivi Östling (KI)
Ulrika Warpman Berglund (KI)
Krister Wennerberg (BRIC-Copenhagen)
Oskar Fernandez-Capetillo (KI)
Per Arvidsson (KI)
Martin Haraldsson (LCBKI)
Thomas Lundbäck (AstraZeneca Göteborg and KI)
Kirsten Tschapalda (AstraZeneca Manchester)
Sean Rudd (KI)
Wei Ouyang (KTH)
Johan Ledin (UU)
Jens Carlsson (UU)
Ola Spjuth (UU)
Carolina Wählby (UU)
Bernhard Schmierer (KI)
Rozbeh Jafari (KI)
Daniel Martinez Molina (Pelago)
Anja Reithmeier (LCBKI)

-Workshop by:

Brinton Seashore-Ludlow (KI)
Jordi Carreras-Puigvert (KI)

-On-site visits to:
Pelago
Sprint Bioscience
Affibody
CBCS
Additional course leader
Latest course evaluation Not available
Course responsible Jordi Carreras Puigvert
Institutionen för medicinsk biokemi och biofysik

jordi.carreras.puigvert@ki.se
Contact person Brinton Seashore-Ludlow
Institutionen för onkologi-patologi

brinton.seashore-ludlow@ki.se