Limits...
Pulmonary squamous cell carcinoma and sorafenib.

Gollard R, Garcia D, Natale R - Clin Case Rep (2014)

Bottom Line: Pulmonary squamous cell carcinomas are not often thought to sensitive to targeted agents, like their cousin the adenocarcinoma of the lung.With appropriate testing of molecular markers, squamous cell carcinomas, like adenocarcinomas of the lung, melanomas, and renal cell carcinomas, may be found to be sensitive to newer, targeted agents.

View Article: PubMed Central - PubMed

Affiliation: Cancer & Blood Specialists of Nevada 2460 W. Horizon Ridge Pkwy., Henderson, Nevada, 89052.

ABSTRACT

Key clinical message: Pulmonary squamous cell carcinomas are not often thought to sensitive to targeted agents, like their cousin the adenocarcinoma of the lung. With appropriate testing of molecular markers, squamous cell carcinomas, like adenocarcinomas of the lung, melanomas, and renal cell carcinomas, may be found to be sensitive to newer, targeted agents.

No MeSH data available.


Related in: MedlinePlus

Nexavar inhibits both VEGFR and PDGFR receptor tyrosine kinases along the RAF/MEK/ERK pathway.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4302627&req=5

fig01: Nexavar inhibits both VEGFR and PDGFR receptor tyrosine kinases along the RAF/MEK/ERK pathway.

Mentions: The patient was not felt to be a candidate for either erlotinib or crizotinib based on the squamous histology; however, sorafenib was felt to possibly have some efficacy for this patient in the second-line setting (Fig.1). Sorafenib is a small molecular inhibitor of several tyrosine protein kinases (vascular endothelial growth factor receptor and platelet-derived growth factor receptor) and Raf kinases (more avidly C-Raf than B-Raf). The rationale is as follows: Some non-V600E BRAF mutations in melanoma cell lines signal through CRAF (gene that encodes enzyme with serine-threonine kinase activity in normal mammalian cells), which, in contrast to BRAF, regulates apoptosis through mitochondrial localization where it binds to Bcl-2 and phosphorylates Bcl-2-associated death promoter (BAD) 9. Sorafenib was found to induce a time-dependent reduction in both BAD phosphorylation and Bcl-2 expression in the D594G/G469E lines through CRAF inhibition. In experimental systems knockdown of CRAF using a lentiviral shRNA suppressed both Bcl-2 expression and induced apoptosis in the D594G melanoma line but not in a V600E-mutated cell line. Based on the in-vitro data, sorafenib, typically used for kidney cancer, was prescribed for our patient. She developed hypertension so the dose had to be reduced from 800 mg to 400 mg/day after 1 month. She subsequently was followed with positron emission tomography (PET) scans. She recurred in the central nervous system (left frontal lobe) and underwent craniotomy followed by whole brain irradiation. She was then evaluated by PET scan. The patient had stabilization of all areas of disease, with decrease in size and uptake in all areas of involvement. She has continued to have stable disease for over 18 months.


Pulmonary squamous cell carcinoma and sorafenib.

Gollard R, Garcia D, Natale R - Clin Case Rep (2014)

Nexavar inhibits both VEGFR and PDGFR receptor tyrosine kinases along the RAF/MEK/ERK pathway.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4302627&req=5

fig01: Nexavar inhibits both VEGFR and PDGFR receptor tyrosine kinases along the RAF/MEK/ERK pathway.
Mentions: The patient was not felt to be a candidate for either erlotinib or crizotinib based on the squamous histology; however, sorafenib was felt to possibly have some efficacy for this patient in the second-line setting (Fig.1). Sorafenib is a small molecular inhibitor of several tyrosine protein kinases (vascular endothelial growth factor receptor and platelet-derived growth factor receptor) and Raf kinases (more avidly C-Raf than B-Raf). The rationale is as follows: Some non-V600E BRAF mutations in melanoma cell lines signal through CRAF (gene that encodes enzyme with serine-threonine kinase activity in normal mammalian cells), which, in contrast to BRAF, regulates apoptosis through mitochondrial localization where it binds to Bcl-2 and phosphorylates Bcl-2-associated death promoter (BAD) 9. Sorafenib was found to induce a time-dependent reduction in both BAD phosphorylation and Bcl-2 expression in the D594G/G469E lines through CRAF inhibition. In experimental systems knockdown of CRAF using a lentiviral shRNA suppressed both Bcl-2 expression and induced apoptosis in the D594G melanoma line but not in a V600E-mutated cell line. Based on the in-vitro data, sorafenib, typically used for kidney cancer, was prescribed for our patient. She developed hypertension so the dose had to be reduced from 800 mg to 400 mg/day after 1 month. She subsequently was followed with positron emission tomography (PET) scans. She recurred in the central nervous system (left frontal lobe) and underwent craniotomy followed by whole brain irradiation. She was then evaluated by PET scan. The patient had stabilization of all areas of disease, with decrease in size and uptake in all areas of involvement. She has continued to have stable disease for over 18 months.

Bottom Line: Pulmonary squamous cell carcinomas are not often thought to sensitive to targeted agents, like their cousin the adenocarcinoma of the lung.With appropriate testing of molecular markers, squamous cell carcinomas, like adenocarcinomas of the lung, melanomas, and renal cell carcinomas, may be found to be sensitive to newer, targeted agents.

View Article: PubMed Central - PubMed

Affiliation: Cancer & Blood Specialists of Nevada 2460 W. Horizon Ridge Pkwy., Henderson, Nevada, 89052.

ABSTRACT

Key clinical message: Pulmonary squamous cell carcinomas are not often thought to sensitive to targeted agents, like their cousin the adenocarcinoma of the lung. With appropriate testing of molecular markers, squamous cell carcinomas, like adenocarcinomas of the lung, melanomas, and renal cell carcinomas, may be found to be sensitive to newer, targeted agents.

No MeSH data available.


Related in: MedlinePlus