News article:
(2007, October 5). Study Suggest Brain Tumors Need Treatment With Multiple ‘Targeted’ Drugs. Drug Week, p. 76
Primary scientific article:
Stommel, J.M. et al. (2007). Co activation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies
Articles citing primary article:
Weil R.J (2008). Incorporating Molecular Tools into Early-Stage Clinical Trials. PLoS Med 5(1): e21
Doi:10.1371/journal.pmed.050021
Guo A. (2008, January 7). Signaling networks assembled by oncogenic EGFR and c-Met. The National Academy of Sciences of the USA
Guirgis H.M (2007). A perspective on tyrosine kinase inhibitors in gastrointestinal stromal tumors and cancer: past and present with emphasis on future and cost. Cancer Therapy Vol 5
Summary:
The primary and secondary article focuses on the study of glioblastoma multiforme (GBM). GBM is an aggressive brain tumor that is nearly always fatal. It’s the most prevalent and highest malignant tumor in the central nervous system of human adults and also the most lethal of many cancers.
What is already known is that receptor tyrosine kinase (RTK) is located on the surface of both normal and cancerous cells and receive signals from the cells location. The signals are chemical “growth factors” directing the cells to divide and grow. Launch of PI3K pathway components appears to be universal in GBM. Activation and signaling received by RTK are transmitted to the cells nucleus by PI3K and behaves abnormally in cancer cells. An epidermal growth factor receptor (EGFR) is a key pathogenic event, with amplification of mutation has been implicated in GBM. Making it a forceful target for therapeutic inhibition. Other RTK’s have been reported to be misrepresented in GBM. Researchers evaluated and sought data that several PI3k activators coexist in glioma cell lines.
The goal of the study is to define the compendium of co activated RTKs in GBM, by using an antibody array technique that will allow simultaneous assessment of the phosphorylation status of 45 RTKs at one time. This test was determined by consequent incubation. Researchers incubated 20 glioma cell lines LN382, SF763, LN18 and HS683 on RTK antibody arrays. Phosphorylations were determined by incubation with horse radish peroxidase. In 19 of the 20 cell lines, three or more RTKs were activated at the same time sending abnormal growth signals to the nucleus. Researchers also explored the therapeutic implications of RTK co activation. By using U87MG glioma cells that constitutively expressed a kinase-dead EGFR vIII (growth factor receptors) at levels comparable to those observed in primary GBMs.
Researchers found that most activated RTKs remained phosphorylated under serum deficiency and in tumor cells. Demonstrating that the RTK activation in the altered cells, is not due to ligands in serum-containing culture media’s. The findings of the study explained clinical responses to RTK-inhibitor monotherapy for many tumor types and look forward to constructive outcomes by combinations of drugs alongside different activated RTKs. The study provided proof for ultimate accomplishment of a therapeutic pattern in human cancer.
(2007, October 5). Study Suggest Brain Tumors Need Treatment With Multiple ‘Targeted’ Drugs. Drug Week, p. 76
Primary scientific article:
Stommel, J.M. et al. (2007). Co activation of Receptor Tyrosine Kinases Affects the Response of Tumor Cells to Targeted Therapies
Articles citing primary article:
Weil R.J (2008). Incorporating Molecular Tools into Early-Stage Clinical Trials. PLoS Med 5(1): e21
Doi:10.1371/journal.pmed.050021
Guo A. (2008, January 7). Signaling networks assembled by oncogenic EGFR and c-Met. The National Academy of Sciences of the USA
Guirgis H.M (2007). A perspective on tyrosine kinase inhibitors in gastrointestinal stromal tumors and cancer: past and present with emphasis on future and cost. Cancer Therapy Vol 5
Summary:
The primary and secondary article focuses on the study of glioblastoma multiforme (GBM). GBM is an aggressive brain tumor that is nearly always fatal. It’s the most prevalent and highest malignant tumor in the central nervous system of human adults and also the most lethal of many cancers.
What is already known is that receptor tyrosine kinase (RTK) is located on the surface of both normal and cancerous cells and receive signals from the cells location. The signals are chemical “growth factors” directing the cells to divide and grow. Launch of PI3K pathway components appears to be universal in GBM. Activation and signaling received by RTK are transmitted to the cells nucleus by PI3K and behaves abnormally in cancer cells. An epidermal growth factor receptor (EGFR) is a key pathogenic event, with amplification of mutation has been implicated in GBM. Making it a forceful target for therapeutic inhibition. Other RTK’s have been reported to be misrepresented in GBM. Researchers evaluated and sought data that several PI3k activators coexist in glioma cell lines.
The goal of the study is to define the compendium of co activated RTKs in GBM, by using an antibody array technique that will allow simultaneous assessment of the phosphorylation status of 45 RTKs at one time. This test was determined by consequent incubation. Researchers incubated 20 glioma cell lines LN382, SF763, LN18 and HS683 on RTK antibody arrays. Phosphorylations were determined by incubation with horse radish peroxidase. In 19 of the 20 cell lines, three or more RTKs were activated at the same time sending abnormal growth signals to the nucleus. Researchers also explored the therapeutic implications of RTK co activation. By using U87MG glioma cells that constitutively expressed a kinase-dead EGFR vIII (growth factor receptors) at levels comparable to those observed in primary GBMs.
Researchers found that most activated RTKs remained phosphorylated under serum deficiency and in tumor cells. Demonstrating that the RTK activation in the altered cells, is not due to ligands in serum-containing culture media’s. The findings of the study explained clinical responses to RTK-inhibitor monotherapy for many tumor types and look forward to constructive outcomes by combinations of drugs alongside different activated RTKs. The study provided proof for ultimate accomplishment of a therapeutic pattern in human cancer.
While reading both the Primary and Secondary article, I noticed that they both had the same content. The secondary article was obviously easier to to read because it was basically a summary of the primary article, and didn’t have as many pages as the primary article. The primary article on the second hand was very difficult to understand. I had to take notes and read over the data several times to finally understand the study that was being held. I prefer the primary article because it had more facts and had figures of the studies and outcomes that were held. When I first read the secondary article I was totally lost. Reading the primary article actually made me understand the secondary article more; giving me the conclusion that both articles are the same. The primary just has more concrete proof about the co activation of RTK and the effects of responses of the tumor cells.
My additional questions are:
1.) Since RTK inhibitors are given to patients with solid tumors how is combination therapy yielding better results?
2.) What are the numbers? Of patients yielding better results?
3.) Could this prolong the life of people with GBM since that type of cancer is so lethal?
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