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Anatomy and Cell Biology
Anatomy and Cell Biology 4461B
Geordie Shepherd

Introductory Lecture What is Translational Cancer Research? • Translational research transforms scientific discoveries arising from laboratory, clinical, or population studies into clinical applications to reduce cancer incidence mobidity and mortality. Translational Continuum Basic Science Discoveries • Promising molecule or gene target • Candidate biomarker • Epidemiological finding Early Translation • Partnerships and collaboration between academia, governement and the indus- try form • Phase I and II trials: Is it safe and does it work better than a placebo? • Translational cancer researchers are mostly in the first two steps Late Translation • Phase III trials: Does it work better than the standard? • Regulatory approval • Commercialization and production • Phase IV trials for additional uses • Costs money to education the public and the health sector Dissemination • Might lead to new drug or diagnostic tool disseminated to health care sector and public Adoption • Used by patients, requires money Hurdles to Translation • Money and time: clinical trials require both these things • MDs and PhDs talk a different language, use different methodologies and are located in different areas • Many do not have any business training and do not understand commercializa- tion • Hard to get human samples Models Used in Cancer Research Tumour Model: Cells, tissues, or animals used to study the development and progression of cancer, and to test new treatments before they are given to humans. Primary cell cultures/ Establish cell lines (1970s) • Allow the systematic assessment of the “Hallmarks of Cancer” • Pros •Simplify problems •Examine specific processes •Tease out molecular mechanisms prior to movement into more complex models •Cons •Does not take complexity into account •Tissue culture artifacts •Models to study specific cell processes are over simplistic •High throughput screens •Libraries of small molecule inhibitors (potential drugs) or RNAi used to discover novel targets • Combined with robotics, imaging and functional cell assays (ex. apopto- sis, cellular invasion, anchorage independent growth) • Potential to query every gene and pathway rapidly •3D Models •Cells cultured in 3D (organotypic) on or in extracellular matrices •Can incorporate other cell types (co-culture) and modify microenviron- mental parameters such as oxygen in order to better recapitulate the tu- mour •Can study the effects of genetic alterations on cell function (structure- function relationships) Animal Models •Better Model of Complexity • More physiologically relevant • Can account for processes that are facilitated by “normal” cells such as angiogenesis (endothelial cells) and immune evasion • Can examine tumour growth and metastasis •Can model cancer initiation and progression •Can support the administration of systemic therapies Xenografts (1970s): When cells of one species are implanted into a different species us- ing immune compromised mice (NOD/SCID, NUDE). Orthotopic site better mimic tumour en- vironment. Examples include in vivo angiogensis assays. •Pros •Allows interrogation in a live animal •Model systems are well characterized •Tumors can grow and metastasize •Cons
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