Although the disease can recur locally by increase of the original tumor size, most of the time the disease return in a metastatic fashion. And when this occurs, there are many implications to be drawn.
Neoplastic transformation assumes acquisition of new functions to the cell. One of the critical function is ability to metastasize, acquisition of MET1 amplification, activity at the Rho gene/RHOA/ROCK but also activity at Vimentin are important processes the cell has to go through to acquire these new functions. These are just some of the aspects.....
Detection of cancer recurrence is as complex as the nature of the Neoplastic process itself!
1. There are activity at promoter genes, most of there activity are silencing of certain promoter genes through methylation. see implications of Methylation of such gene as TGF Beta, SMAD4 and even FBXO32, Cyclin D, 14.3.3. etc (Aberrant Methylation)
2. Suppression of E-Cadherin which for some poise the cell for Migration. If this occur through MSK1, it may also impact p38MAPK and restart tumor induced by the MAPK pathway amplification, and inducing VEGF induced migration of cells. This phenomena could be worse in these disease when Anti-VEGF is not usually used (since we use Anti-VEGF only in certain diseases--if we continue to use clinical trial as our basis foe adoption of a treatment)
3.Coming back to methylation, it has been stricking that certain genes are not remarkably expressed in certain cancer cells. ie. "
"DAB2 mRNA is expressed in normal ovarian epithelial cells but is down-regulated or absent from ovarian carcinoma cell lines."wikipedia This seems to involve somehow the SMAD
do remember "DAB2 has been shown to interact with C-src tyrosine kinase, Cdk1, Src, LRP2, DVL3, PIN1, MYO6, DVL2, DAB2IP, Mothers against decapentaplegic homolog 3 and Mothers against decapentaplegic homolog 2." wikipedia
note many things please
attachment opportunity offered by C-Src
involvement of Cdk1 affecting cell proliferation and of course SMAD.... Terget therapy in mind!
Decreased expression of 14-3-3 sigma is associated with advanced disease in human epithelial ovarian cancer: its correlation with aberrant DNA methylation.Akahira J1, Sugihashi Y (READ THE ARTICLE)
4. FOR RECURRENT DISEASE, PERSISTENCE OF CERTAIN INDUCERS (G-PROTEINS) PROPPING PUSH TO REESTABLISH A TUMOR PROCESS, OR LACK OF CERTAIN INHIBITORS TO GERB2 INVOLVEMENT SUCH AS SPRY-2. (MARKING AMPLIFICATION OF GERB2 IN SURVIVOR MONITORING!)
WILSON ET AL "HER-2 overexpression in the context of the mesenchymal MDA-MB-231 breast cell line potentiated the TGF-beta induced pro-invasive and pro-metastatic gene signature." MARKING THE IMPORTANCE OF TGF IN HER-2 POSITIVE CANCERS!
5.In BRCA-1 pt
we have already stress the importance of following PTPN2 as it impacts TGF, Paxillin, and mainly SHC1, the regulator of Apoptosis!
6. And if you are following Vimentin, weel check the AXL, decrease of RAB25, and the Integrin Beta subunit, these to gauge Epithelia-mesothelial transformation, an important step to acquisition of metastatic potential
well I stop here, survivors are deemed expensive because of this complexity and gene monitoring, weel we are not up to it yet, we chose head in the sand...And I am not talking yet about persistant of viral compounds that may also be important in metastatic potential in survivors. What we need is a better organization of pouring info coming to us ...."sparsely-disconnected" .