Britney Porter, Sandra Nguyen, Eduardo Vargas and Samender Singh Randhawa

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?

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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.

• 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.

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.

The CellSearch® Profile Kit allows standardized and automated immunomagnetic collection and enrichment of circulating epithelial cells from whole blood.

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

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.

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.

KINASE INHIBITION

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.

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).

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.

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.

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?

Sourceshttp://www.personalgenomes.org/mission.htmlhttp://www.personalizedmedicinecoalition.org/science/topics/personalized-disease-managementhttp://www.ageofpersonalizedmedicine.org/personalized_medicine/case/http://www.aacc.org/publications/cln/2011/october/Pages/PersonalizedMedicine.aspxhttp://www.dana-farber.org/Research/Featured-Research/Profile-Somatic-Genotyping-Study.aspxhttp://www.mayomedicallaboratories.com/articles/communique/2011/01.htmlhttp://www.futuremedicine.com/doi/full/10.2217/pme.12.104https://docs.google.com/viewer?a=v&q=cache:JhuZfuMBsDUJ:www.personalizedmedicinecoalition.org/sites/default/files/personalmed_backgrounder.pdf+personalized+medicine+techniques+cancer+treatment&hl=en&gl=us&pid=bl&srcid=ADGEESgdNmo-sJ5twRYZf0RgzDQD-OKvvrmAH-8wU8ykmxekZlOCQ9PE8HYyOJ9C-gj_HBAK7HIwYk7rqnT-hNH37eVdr4xeefWnHGxlNHuiUcnGcEeDjHyw8VsrPHzRx1t8t_ud-0rb&sig=AHIEtbSH_hFnO3WRbbXDiBtI2udZ0Y8Qaw