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What techniques are utilized to develop a personalized diagnosis for cancer
patients?
Can you envision such techniques occurring routinely for every patient in the
foreseeable future?
Britney Porter, Sandra Nguyen, Eduardo Vargas and Samender Singh Randhawa
Techniques
• Personalized medicine, when coupled with personal
pharmacogenetics, is a unique approach that may be well
suited for the health challenges we face in the new
millennium.
• Some experts argue that high-throughput whole genome
sequencing holds the greatest potential, while others are
more excited about emerging technologies like circulating
tumor cell and microRNA analyses.
MicroRNA sequencing (miRNA-seq), a type of RNA-Seq, is the massively
parallel high-throughput DNA sequencing to sequence miRNAs. miRNA-seq
allows researchers to examine tissue specific expression patterns, disease
associations, isoforms of miRNAs, and to discover previously uncharacterized
miRNAs.
• Circulating tumor
cells (CTCs) are cells that have
shed into the vasculature from a
primary tumor and circulate in
the bloodstream. CTCs thus
constitute seeds for subsequent
growth of additional tumors
(metastasis) in vital distant
organs, triggering a mechanism
that is responsible for the vast
majority of cancer-related
deaths.
The CellSearch® Epithelial Cell Kit enables the immunomagnetic
selection, identification and enumeration of circulating epithelial
cells in peripheral blood. The kit contains a ferrofluid-based capture
reagent and immunofluorescent staining reagents. It targets the
EpCAM antigen for capturing the circulating epithelial cells. EpCAM
is a epithelial differentiation antigen that is expressed on almost
all carcinomas. Its constitutional function is being elucidated.
EpCAM is a carcinoma-associated antigen
The CellSearch® Profile Kit allows standardized and
automated immunomagnetic collection and enrichment of
circulating epithelial cells from whole blood.
Compare the Food and Drug Administration-approved CellSearch Epithelial Kit (CEK)
to a simplified CTC capture method, CellSearch Profile Kit (CPK).
The CPK method isolates a greater number of cells than the CEK method
This technology potentially has a large number of applications in investigating the
biology of metastatic cancer and in drug development in which it can be used to
identify predictive biomarkers, mechanisms of resistance.
KINASE INHIBITION
What is a kinase?
It is a type of enzyme that transfers phosphate groups from high -energy donor
molecules to specific substrates. One large group of kinases are called protein kinases.
What is protein kinases?
It acts and modifies the activity of specific proteins. They are mainly used as
transmit signals to control the complex processes in cells.
What are protein kinase inhibitors?
They are a type of enzyme inhibitor that blocks or stops the action of one or
more protein kinases. Therefore, they are able to be subdivided by the amino acids.
They can interfere with the repair of DNA double-strand breaks.
An example of a kinase inhibitor is dasatinib (PLX5568). It is often used in the treatment of
cancer and inflammation. The kinase inhibitor is currently being tested for treatment of
polycystic kidney disease as well as pain.
Many other kinase inhibitors are being tested, such as ponatinib
(AP24534). This tyrosine kinase inhibitor has recently shown to be helpful
in patients of myeloid leukemia (CML) and acute lymphoblastic leukemia
(ALL).
Some of the kinase inhibitors used in treating cancer are inhibitors of
tyrosine kinases.
The effectiveness of these kinase inhibitors on different types of cancer
vary in patients. Thus, it is crucial to research the patient’s background in
order to know of it’s effectiveness.
Anaplastic Lymphoma Kinase Inhibition in Non–Small-Cell Lung Cancer
Oncogenic genes consisting anaplastic lymphoma kinase (ALK) are present in a
subgroup of non–small-cell lung cancers, representing 2 to 7% of such tumors. They
explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase
clinical trial of crizotinib, an orally available small-molecule inhibitor of the ALK
tyrosine kinase.
These patients were enrolled in an expanded cohort study instituted after phase 1
dose escalation had established a recommended crizotinib dose of 250 mg twice
daily in 28-day cycles.
Patients with ALK rearrangements tended to be younger than those without the
rearrangements, and At a mean treatment duration of 6.4 months, the overall
response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1
confirmed complete response); 27 patients (33%) had stable disease.
CONCLUSIONS The inhibition of ALK in lung tumors with the ALK rearrangement
resulted in tumor shrinkage or stable disease in most patients.
Techniques occurring routinely for every
patient in the foreseeable future?
• It took $3 billion and 13 years to sequence the first draft of the human
genome. During that time, sequencing technology evolved from the
manual Sanger method using radioactive labels to automated
sequencing using color-coded fluorescent dyes.
• The whole-genome sequencing costs fell from $100-300 million in 2001
to about $10 million in 2007, as a result of the exponential increase in
performance of computer technology for the past 40 years;
“Today, one of our biggest goals is to cut the cost of
sequencing an entire human genome to $1,000 or
less. This advance will pave the way for each person’s
genome to be sequenced as part of the standard of
care, leading to a revolution in the practice of
”
medicine.
Francis S. Collins, M.D., Ph.D. Director, National
Institutes of Health
[Alzheimer’s] As of 2012, more
than 1000 clinical trials
[NIH] have been or are being
conducted to find ways to treat
the disease, but it is unknown
if any of the tested treatments
will work.
The Personal Genome Project
Based at Harvard University and supported by a spectrum of government agencies,
foundations, academic institutions and corporations.
The mission of the Personal Genome Project is to encourage the development of
personal genomics technology and practices that:
• are effective, informative, and responsible
• yield identifiable and improvable benefits at manageable levels of risk
• are broadly available for the good of the general public
“Promoting personalized medicine means
making sure the FDA medical product centers
work together as a team to get safe and effective
new treatments to patients as quickly as
possible.
” FDA Innovation Report, October 5, 2011
Some of the challenges faced by personalized
medicine
●
Science companies, healthcare
providers, payers and policy makers
must be in sync so that they can
progress
●
Fortunately the FDA is currently
playing a key role in advancing
personalized medicine.
●
Many questions also develop when we think of personalized medicine:
●
How will this effect patient confidentiality ?
●
Can insurance companies limit the coverage based on genomic sequence?
●
Will insurance providers have limited information of patients' genomic sequence?
●
Should improved medical education or patient education be covered?
Sources
http://www.personalgenomes.org/mission.html
http://www.personalizedmedicinecoalition.org/science/topics/personalized-diseasemanagement
http://www.ageofpersonalizedmedicine.org/personalized_medicine/case/
http://www.aacc.org/publications/cln/2011/october/Pages/PersonalizedMedicine.as
px
http://www.dana-farber.org/Research/Featured-Research/Profile-SomaticGenotyping-Study.aspx
http://www.mayomedicallaboratories.com/articles/communique/2011/01.html
http://www.futuremedicine.com/doi/full/10.2217/pme.12.104
https://docs.google.com/viewer?a=v&q=cache:JhuZfuMBsDUJ:www.personalizedme
dicinecoalition.org/sites/default/files/personalmed_backgrounder.pdf+personalized
+medicine+techniques+cancer+treatment&hl=en&gl=us&pid=bl&srcid=ADGEESgdN
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