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Lecture 1

BIOL 4010 Lecture Notes - Lecture 1: Chronic Myelogenous Leukemia, Imatinib, Metastasis

Course Code
BIOL 4010

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Receptor tyrosine kinases have similar kinase domains, they have different tails to bind different
types of ligands. Ligand binds receptors dimerize
The nature of cancer
Hippocrates: beginning of recorded medicine, the first physician to recognize differences
between benign and malignant tumors. He described cancers in different body sites. Swollen
blood vessels around a malignant tumor reminded him of a crab Karkinos = carcinos =
carcinoma = cancer
Scientists were interested in cancer since beginning of history
The time in history during which we had the chance to understand cancer is limited to the 20th
century (from the 70s). before that we had no clue about cancer. The first treatment of cancer is
limited to the second half of the 20th century (1946 was the first time that kids were treated for
cancer with drugs, today 95% of the kids that have this cancer will survive).
Everything we know is mostly recent
How the understanding of molecular aspect of cancer lead us to developing certain drugs such
as Gleevec (chronic myelogenous leukemia CML). Gleevec works on the molecular level
The initial force of the revolution: a mistake in the 60s: policy makers= infectious diseases are
out of the way, antibiotics, especially vaccinations, made the infectious diseases not relevant
anymore switched the funding to cancer research. We earned the ability to study cancer
Yin and yang: describe how opposite forces can be working together as complementary forces in
the natural world (homeostasis, = every enzyme that evolved has an antagonist enzyme ex,
kinases and phosphatases, they have opposite activity)
Homeostasis is key for normal healthy organism
Two forces that are opposite: proliferation and cell death (both controlled by positive and
negative factors)
Proliferation: positively controlled by growth factors, negatively by growth suppressors. To
maintain proliferation at a certain level
Cell death (apoptosis): death factors and death suppressors.
Each of them have opposite effect in the body
Adults have a relatively constant number of cells, we make a lot of cells but also a lot of cells die
Tumor: disruption of homeostasis
In adults: the ratio of cells made to cells dying must be 1:1
In a tumor, the ratio is >1:1
It doesn’t have to be a big ratio difference; a tumor can form over decades. Could be 1.001:1
(1% increase) can create a tumor. This process is usually mediated by too much proliferation and
too little death but its usually a combination of both. Tumors usually have too much growth
(more growth factors + less suppressors/cell loses sensitivity to them) and too little death (more
death suppressors and less death factors) = result of homeostasis disruption
Small change can lead to a tumor
3 different types of tumors: benign, malignant, metastasis
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