d(GC) - Association of Biotechnology and Pharmacy
d(GC) - Association of Biotechnology and Pharmacy
d(GC) - Association of Biotechnology and Pharmacy
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Current Trends in <strong>Biotechnology</strong> <strong>and</strong> <strong>Pharmacy</strong><br />
Vol. 6 (2) 119-144 April 2012, ISSN 0973-8916 (Print), 2230-7303 (Online)<br />
genotyping tests for families <strong>of</strong> certain<br />
geographical or ethnic origins (112). Of interest<br />
to Panama are the mutations observed in high<br />
frequency in the Hispanic populations <strong>of</strong><br />
Colombia, well as those observed among Afro-<br />
American women, as nearly10% <strong>of</strong> Panama’s<br />
population identifies as being <strong>of</strong> African descent<br />
(117).<br />
HER2 testing : Several US-FDA approved tests<br />
exist for analysis <strong>of</strong> HER2 expression in breast<br />
cancer biopsies, demonstration <strong>of</strong> which is a<br />
necessary step before women can be prescribed<br />
trastuzumab or lapatinib. These tests are based<br />
on detection <strong>of</strong> the HER2 protein or quantification<br />
<strong>of</strong> HER2 gene copy number <strong>and</strong> include the Dako<br />
Anti-HER2 IHC System (the Hercep Test) <strong>and</strong><br />
the Ventana Medical Systems Inform Dual ISH<br />
test.<br />
KIT testing <strong>and</strong> c-kit <strong>and</strong> pdgfra genotyping :<br />
Somatic mutations in exons 9, 11, 13 <strong>and</strong> 17 <strong>of</strong><br />
c-kit can be evaluated using PCR-based assays<br />
<strong>and</strong> direct cycle sequencing <strong>of</strong> the PCR product.<br />
Patient samples with non-mutated c-kit can then<br />
be evaluated for pdgfra gene mutations in exons<br />
12 <strong>and</strong> 18 (97, 118). Immunohistochemistry for<br />
KIT expression can be performed using the<br />
DakoCytomation c-Kit pharmDx product (US-<br />
FDA approved) <strong>and</strong> other commercially available<br />
anti-KIT monoclonal antibodies.<br />
Commercial kits : Several companies <strong>of</strong>fer<br />
products for genetic analysis <strong>and</strong><br />
pyrosequencing, the major ones being QIAGEN<br />
(genetic analysis for KRAS, EGFR, BRAF,<br />
PIK3CA <strong>and</strong> others, <strong>and</strong> pyrosequencing for<br />
BRAF, KRAS <strong>and</strong> EGFR) <strong>and</strong> Roche Molecular<br />
Diagnostics (genetic analysis for KRAS, EGFR<br />
<strong>and</strong> BRAF). Wang et al. (119) review several<br />
commercial products for KRAS mutation testing<br />
<strong>and</strong> note the importance <strong>of</strong> identifying a goldst<strong>and</strong>ard<br />
assay to determine reference<br />
st<strong>and</strong>ards. MLC Holl<strong>and</strong> sells multiplex ligationdependent<br />
probe amplication kits for BRCA1,<br />
BRCA2, CHD1, PTEN, MLH1, MSH2, APC,<br />
MSH6 <strong>and</strong> DPD analysis. The SNaPshot(R)<br />
Multiplex System from Applied Biosystems has<br />
Developing world personalized cancer medicine<br />
133<br />
been applied for SNP analysis <strong>of</strong> MLH1 <strong>and</strong><br />
MSH2 (120) <strong>and</strong> KRAS mutations in codons 12<br />
<strong>and</strong> 13 (103).<br />
Other resources : The National Center for<br />
<strong>Biotechnology</strong> Information (NCBI) hosts a useful<br />
database called GeneTests (http://<br />
www.ncbi.nlm.nih.gov/sites/GeneTests/). Its<br />
main feature is the listing <strong>of</strong> tests <strong>of</strong>fered in the<br />
USA <strong>and</strong> globally for a large number <strong>of</strong> genetic<br />
disorders. It is organized by genetic disorder <strong>and</strong><br />
describes laboratories which <strong>of</strong>fer testing <strong>and</strong> the<br />
method <strong>of</strong> testing employed, if a variety <strong>of</strong><br />
protocols are available. It can be searched by<br />
disease or gene name <strong>and</strong> also has links to<br />
GeneReviews, which are peer-reviewed<br />
descriptions <strong>of</strong> genetic diseases.<br />
Conclusion<br />
Cancer has overtaken infectious disease<br />
as the leading cause <strong>of</strong> death in the developing<br />
world. Of significance are lung/bronchial, liver,<br />
stomach, esophageal, colorectal, breast <strong>and</strong><br />
cervical cancers in adults, <strong>and</strong> leukemia, Non-<br />
Hodgkin lymphoma, brain <strong>and</strong> nervous system<br />
cancers, kidney cancer <strong>and</strong> Hodgkin lymphoma<br />
in children (16), with the likelihood <strong>of</strong> surviving<br />
cancer being decreased for the developing world<br />
for Hodgkin <strong>and</strong> non-Hodgkin lymphoma;<br />
multiple myeloma; thyroid, prostate <strong>and</strong> testicular<br />
cancer, or if you are less than 14 years <strong>of</strong> age.<br />
Many low- <strong>and</strong> middle-income countries<br />
lack even basic resources for diagnosing <strong>and</strong><br />
treating cancer, but others with better developed<br />
medical <strong>and</strong> scientific infrastructure, such as<br />
Panama in Central America, are beginning to<br />
apply personalized medicine for pre-symptomatic<br />
risk assessment, diagnosis, prognosis <strong>and</strong><br />
treatment <strong>of</strong> solid tumors <strong>and</strong> lymphoproliferative<br />
malignancies. In Figure 1, we list a number <strong>of</strong><br />
initiatives to exp<strong>and</strong> the existing program <strong>of</strong><br />
personalized medicine in that country.<br />
Even in regions with better scientific <strong>and</strong><br />
medical resources, however, the application <strong>of</strong><br />
personalized medicine for cancer is being