News Article:
Health Day (Apr 26, 2007)"Scientists spot mechanism behind lung cancer drug resistance."
Primary Scientific News Article:
Science (May18, 2007) Vol.316.no.5827,pp1039-1043
Gefitinib and erlotinib are epidermal growth factor receptor kinase inhibitors that have shown to be effective treatments for lung cancers with EGFR (epidermal growth factor receptor) activating mutations. Unfortunately we see that many of these tumors ultimately become drug resistant. Researchers identified a MET amplification that was found in many lung cancer specimens that had developed a drug resistance to either gefitinib or erlotinib. This MET amplification causes gefitinib resistance by ERBB3 activating P13K.
Researchers investigated whether activation of another receptor was aiding this resistance. They used a phospho- receptor tyrosine kinase to compare the effects of gefitinib on lung cancer cells. The resistant cells phosphorilation of MET, ERBB3, and EGFR continued at higher levels in the presence of gefitinib. In contrast to the non-mutated cells which responded to the presence of gefitinib.
They also preformed a genome-wide copy analysis and found that the resistant cells contains a MET amplification. Researchers then later discovered that MET amplification activated ERBB3 signaling causing gefitinib resistance. These findings may potentially have clinical importance to NSCLC patients who develop resistance to either gefitinib or erlotinib.
The news article and primary research article were similar in their “grand message” but the primary research article was more thorough in comparison to the news article. The news article was helpful in summarizing the overall point in the researchers findings to the general public.
Remaining questions:
Are there other types of EGFR that could aid in the treatment in lung cancer?
What could physicians do differently in helping treat drug resistant patients?
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3 comments:
It really is unfortunate that the tumors end up being drug resistant. But good thing the researchers that investigated this issue are now a step closer since they discovered that MAT amplification activated ERBB3. I also wonder if they have any other epidermal growth factor receptors available that can help in the treatment of lung cancer.
Drug Resistant Lung Cancer
Primary research:
Science (2007) Vol.316.no.5827, pp1039-1043
Posts sharing a common thread:
GPRC5A Can be the Key to Lung Cancer.
Primary Research:
Tao, Q. et. al (2007). Identification of the Retinoic Acid- Inducible Gprc5aAs a New Lung Tumor Suppressor Gene. Journal of the National Cancer Institute, 99(22), 1668-1682.
LKB1 Kinase as a Tumor Suppressor.
Primary Research:
Upadhyay, S. et. al (2006). LKB1/STK11 Suppresses Cyclooxygenase- 2 Induction and Cellular Invasion through PEA3 in Lung Cancer. Cancer Research, Vol. 66, pp. 7870-7879.
The blog posted as Drug Resistant to Lung Cancer, caught my eye. I have read about the activation of the pathways leading to cancers, but never about those pathways controlling the effect drugs have on cancer cells. The name of the primary article is unknown.
The common thread of the posts is lung cancer. The blog posted titled, GPRC5A Can Be the Cure to Lung Cancer, mentions a cure for lung cancer. GPRC5A is a tumor suppressor gene; its loss of function can cause cancer. The blog post GPRC5A can be... explains that by recovering the GPRC5A gene, scientists may have a way of suppressing the invasion and uncontrolled proliferation of lung cancer cells. The post Drug Resistant… mentions the blocking of the action of the drug geftinib in its use to treat lung cancer. The researchers of Drug Resistant… wanted to know what was causing lung cancer cells to resist the drugs. The amplification of MET activates ERBB3 signaling, which in turn resists the drugs and activate the PI3K pathway. The mutant form of the LKB1 kinase cannot inhibit PEA3. PEA3 which is a transcription factor is allowed to activate the COX- 2 pathway, which leads to cell invasion and metastasis. The post does not mention the GPRC5A gene and the LKB1 kinase are gatekeepers. From what I have learned in class a gatekeeper maintains cell survival and proliferation, its mutant form cause uncontrolled cell proliferation.
How doe the ERBB3 pathway cause a resistance to geftinib?
Will there be new drugs that can inhibit the effects of amplified MET?
Drug Resistant Lung Cancer
Primary research:
Science (2007) Vol.316.no.5827, pp1039-1043
Posts sharing a common thread:
GPRC5A Can be the Key to Lung Cancer.
Primary Research:
Tao, Q. et. al (2007). Identification of the Retinoic Acid- Inducible Gprc5aAs a New Lung Tumor Suppressor Gene. Journal of the National Cancer Institute, 99(22), 1668-1682.
LKB1 Kinase as a Tumor Suppressor.
Primary Research:
Upadhyay, S. et. al (2006). LKB1/STK11 Suppresses Cyclooxygenase- 2 Induction and Cellular Invasion through PEA3 in Lung Cancer. Cancer Research, Vol. 66, pp. 7870-7879.
The blog posted as Drug Resistant to Lung Cancer, caught my eye. I have read about the activation of the pathways leading to cancers, but never about those pathways controlling the effect drugs have on cancer cells. The name of the primary article is unknown.
The common thread of the posts is lung cancer. The blog posted titled, GPRC5A Can Be the Cure to Lung Cancer, mentions a cure for lung cancer. GPRC5A is a tumor suppressor gene; its loss of function can cause cancer. The blog post GPRC5A can be... explains that by recovering the GPRC5A gene, scientists may have a way of suppressing the invasion and uncontrolled proliferation of lung cancer cells. The post Drug Resistant… mentions the blocking of the action of the drug geftinib in its use to treat lung cancer. The researchers of Drug Resistant… wanted to know what was causing lung cancer cells to resist the drugs. The amplification of MET activates ERBB3 signaling, which in turn resists the drugs and activate the PI3K pathway. The mutant form of the LKB1 kinase cannot inhibit PEA3. PEA3 which is a transcription factor is allowed to activate the COX- 2 pathway, which leads to cell invasion and metastasis. The post does not mention the GPRC5A gene and the LKB1 kinase are gatekeepers. From what I have learned in class a gatekeeper maintains cell survival and proliferation, its mutant form cause uncontrolled cell proliferation.
How doe the ERBB3 pathway cause a resistance to geftinib?
Will there be new drugs that can inhibit the effects of amplified MET?
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