Lani
07-29-2010, 02:03 PM
her2 sure seems to hang around with dangerous neighbors
on the same nearby segment of DNA to her2 are GRB7 (see my previous post) which may, even more than her2) be responsible for the aggressive behavior usually attributed to her2 and now it turns out another neighboring gene or the sequence of DNA near her2 is also an oncogene. SO many bad actors, all in the same neighborhood...no wonder her2 gets blamed all the time and may not even always be the culprit. Even if it isn't, it was lucky Drs. Slamon et all noticed its amplification was associated with a subgroup of bc patients with more aggressive disease which recurred earlier and was associated with decreased survival compared with other patients without the amplification.
It seems they already have been working on drugs targetting C35, so more ammunition may be coming for those for whom herceptin doesn't do it or who become resistant to herceptin.
The more we understand the disease the better ammunition and combinations of ammunition we can come up with!
Potential New Treatment for Common Form of Breast Cancer
[Breakthrough Breast Cancer]
Scientists from the Breakthrough Breast Cancer Research Unit at the University of Edinburgh have discovered a potential new way to treat a common form of breast cancer which affects 9,000 UK women each year.
The team are the first to identify a gene's key role in causing the spread of HER2 positive breast cancer to other parts of the body. The gene is called C35 and becomes overactive in this type of tumour.
What makes the discovery even more exciting is that there are drugs in development which could potentially kill cancer cells which rely on this gene. They do this by disabling a protein associated with the gene, which stops it from working. It is thought this type of drug would therefore be a new treatment for HER2 positive breast cancer and save the lives of women with this type of the disease. The research is published today online in the British Journal of Cancer.
HER2 positive breast cancer affects around 9,000 women in the UK each year and 800 women in Scotland - making up about 20% of all breast cancer cases. While it can be treated with the targeted treatment, Herceptin (trastuzumab), that drug does not work for all patients, and can stop working for others after time. This means new treatments are vitally needed to save lives of women with this type of the disease.
Research leader Dr Elad Katz, from the Breakthrough Breast Cancer Research Unit, said: "With all cancers, the key is working out how they form and spread. Identifying this gene's key role in the spread of this type of breast cancer is a significant finding.
"We are at an early stage, but there is now a real possibility there could be a new treatment for women with HER2 positive breast cancer."
Professor David Harrison, Director of the Breakthrough Breast Cancer Research Unit at the University of Edinburgh, said: "This is an important development because we now know one of the key triggers to the spread this type of cancer. It is exciting to know there is a drug out there which could potentially stop this process happening and save the lives of women with breast cancer.
"We now need to do more work in the lab to prove this concept before we can start patient trials."
REPRINT: ABSTRACT: A gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syk
[British Journal of Cancer]
Background: C35 is a 12 kDa membrane-anchored protein endogenously over-expressed in many invasive breast cancers. C35 (C17orf37) is located on the HER2 amplicon, between HER2 and GRB7. The function of over-expressed C35 in invasive breast cancer is unknown.
Methods: Tissue microarrays containing 122 primary human breast cancer specimens were used to examine the association of C35 with HER2 expression. Cell lines over-expressing C35 were generated and tested for evidence of cell transformation in vitro.
Results: In primary breast cancers high levels of C35 mRNA expression were associated with HER2 gene amplification. High levels of C35 protein expression were associated with hallmarks of transformation, such as, colony growth in soft agar, invasion into collagen matrix and formation of large acinar structures in three-dimensional (3D) cell cultures. The transformed phenotype was also associated with characteristics of epithelial to mesenchymal transition, such as adoption of spindle cell morphology and down-regulation of epithelial markers, such as E-cadherin and keratin-8. Furthermore, C35-induced transformation in 3D cell cultures was dependent on Syk kinase, a downstream mediator of signalling from the immunoreceptor tyrosine-based activation motif, which is present in C35.
Conclusion: C35 functions as an oncogene in breast cancer cell lines. Drug targeting of C35 or Syk kinase might be helpful in treating a subset of patients with HER2-amplified breast cancers.
on the same nearby segment of DNA to her2 are GRB7 (see my previous post) which may, even more than her2) be responsible for the aggressive behavior usually attributed to her2 and now it turns out another neighboring gene or the sequence of DNA near her2 is also an oncogene. SO many bad actors, all in the same neighborhood...no wonder her2 gets blamed all the time and may not even always be the culprit. Even if it isn't, it was lucky Drs. Slamon et all noticed its amplification was associated with a subgroup of bc patients with more aggressive disease which recurred earlier and was associated with decreased survival compared with other patients without the amplification.
It seems they already have been working on drugs targetting C35, so more ammunition may be coming for those for whom herceptin doesn't do it or who become resistant to herceptin.
The more we understand the disease the better ammunition and combinations of ammunition we can come up with!
Potential New Treatment for Common Form of Breast Cancer
[Breakthrough Breast Cancer]
Scientists from the Breakthrough Breast Cancer Research Unit at the University of Edinburgh have discovered a potential new way to treat a common form of breast cancer which affects 9,000 UK women each year.
The team are the first to identify a gene's key role in causing the spread of HER2 positive breast cancer to other parts of the body. The gene is called C35 and becomes overactive in this type of tumour.
What makes the discovery even more exciting is that there are drugs in development which could potentially kill cancer cells which rely on this gene. They do this by disabling a protein associated with the gene, which stops it from working. It is thought this type of drug would therefore be a new treatment for HER2 positive breast cancer and save the lives of women with this type of the disease. The research is published today online in the British Journal of Cancer.
HER2 positive breast cancer affects around 9,000 women in the UK each year and 800 women in Scotland - making up about 20% of all breast cancer cases. While it can be treated with the targeted treatment, Herceptin (trastuzumab), that drug does not work for all patients, and can stop working for others after time. This means new treatments are vitally needed to save lives of women with this type of the disease.
Research leader Dr Elad Katz, from the Breakthrough Breast Cancer Research Unit, said: "With all cancers, the key is working out how they form and spread. Identifying this gene's key role in the spread of this type of breast cancer is a significant finding.
"We are at an early stage, but there is now a real possibility there could be a new treatment for women with HER2 positive breast cancer."
Professor David Harrison, Director of the Breakthrough Breast Cancer Research Unit at the University of Edinburgh, said: "This is an important development because we now know one of the key triggers to the spread this type of cancer. It is exciting to know there is a drug out there which could potentially stop this process happening and save the lives of women with breast cancer.
"We now need to do more work in the lab to prove this concept before we can start patient trials."
REPRINT: ABSTRACT: A gene on the HER2 amplicon, C35, is an oncogene in breast cancer whose actions are prevented by inhibition of Syk
[British Journal of Cancer]
Background: C35 is a 12 kDa membrane-anchored protein endogenously over-expressed in many invasive breast cancers. C35 (C17orf37) is located on the HER2 amplicon, between HER2 and GRB7. The function of over-expressed C35 in invasive breast cancer is unknown.
Methods: Tissue microarrays containing 122 primary human breast cancer specimens were used to examine the association of C35 with HER2 expression. Cell lines over-expressing C35 were generated and tested for evidence of cell transformation in vitro.
Results: In primary breast cancers high levels of C35 mRNA expression were associated with HER2 gene amplification. High levels of C35 protein expression were associated with hallmarks of transformation, such as, colony growth in soft agar, invasion into collagen matrix and formation of large acinar structures in three-dimensional (3D) cell cultures. The transformed phenotype was also associated with characteristics of epithelial to mesenchymal transition, such as adoption of spindle cell morphology and down-regulation of epithelial markers, such as E-cadherin and keratin-8. Furthermore, C35-induced transformation in 3D cell cultures was dependent on Syk kinase, a downstream mediator of signalling from the immunoreceptor tyrosine-based activation motif, which is present in C35.
Conclusion: C35 functions as an oncogene in breast cancer cell lines. Drug targeting of C35 or Syk kinase might be helpful in treating a subset of patients with HER2-amplified breast cancers.