PHY3181 Lecture Notes - Lecture 13: Transrectal Ultrasonography, Blood Test, Rectal Examination
30 Jun 2018
School
Department
Course
Professor
Lecture 20: reproductive cancers – prostate
• 1 in 2 men and 1 in 3 women will be
diagnosed
• Cancer is the leading cause of death in
Australia
• Caused by a series of mutations to give
a growth advantage
• Mutations typically occur in a tumour
suppressor first
• Second hit in an oncogene
• Note that one mutations will not
normally cause cancer
Defining feature: metastasis – defining feature
of cancer is the ability to spread to surrounding
areas, or different part of the body. Cancer
cells that do not spread beyond the immediate
area in which they arise are said to be benign
ie. They are typically not dangerous.
Hallmarks of cancer
1. Sustaining proliferative signalling
2. Evading growth suppressors
3. Activating invasion and metastasis
4. Enabling replicative immortality
5. Inducing angiogenesis
6. Resisting cell death
New hallmarks of cancer
1. Deregulating cellular energetics
2. Genome instability and mutation
3. Avoiding immune destruction
4. Tumour promoting inflammation
The more mutations that a cancer has the
more aggressive. Some mutations will promote
further genetic instability eg mutations in DNA
repair genes eg in BRACA2
Cells of the tumour microenvironment
• Immune cells
• Fibroblasts
• Blood vessels
• Endothelial cell
• Pericyte
• Cancer stem cells
• Neuroendocrine cells
• These all communicate, there is
reciprocal signalling and cell
interactions often fuelling cancer eg
by sending growth factors to each
other
• The microenvironment drives the
hallmarks of cancer
Therapeutic approaches to cancer (drug
target)
• EGFR inhibitors sustaining
proliferative signalling
• Cyclin-dependent kinase inhibitors ->
evading growth suppresses
• Immune activating anti-CTL4 mAb
avoiding immune destruction
• Telomerase inhibitors enabling
replicative immortality
• Selective anti-inflammatory drugs
tumour promoting inflammation
• Inhibitors of HGF/c-Met activating
invasion and metastasis
• Inhibitors of VEGF signalling
inducing angiogenesis
• PARP inhibitors genome instability
and mutation
• Proapoptotic BMH3 mimetic
resisting cell death
• Aerobic glycolysis inhibitors
deregulating cellular energetics
*************************************
Usually cancers are caused by somatic
mutations, however they can be from germline
mutations (genetic). Mutations in BRCA1/2 can
be inherited implicated in breast and
prostate cancer.
*************************************
Treatment resistance – this commonly occurs
with cancer drugs. Therapy resistance occurs
when cancers have been responding to a
therapy suddenly begin to grow. In order
words the cancer cells are resisting the effects
of the drug being used the tumour will
regress to almost undetectable levels, but then
Document Summary
Lecture 20: reproductive cancers prostate: 1 in 2 men and 1 in 3 women will be diagnosed, cancer is the leading cause of death in. Australia: caused by a series of mutations to give a growth advantage, mutations typically occur in a tumour suppressor first, second hit in an oncogene, note that one mutations will not normally cause cancer. Defining feature: metastasis defining feature of cancer is the ability to spread to surrounding areas, or different part of the body. Cancer cells that do not spread beyond the immediate area in which they arise are said to be benign ie. they are typically not dangerous. Hallmarks of cancer: sustaining proliferative signalling, evading growth suppressors, activating invasion and metastasis, enabling replicative immortality, resisting cell death. New hallmarks of cancer: deregulating cellular energetics, genome instability and mutation, avoiding immune destruction, tumour promoting inflammation. The more mutations that a cancer has the more aggressive.
