Although Ramucirumab a " fully human monoclonal antibody (IgG1) developed for the treatment of solid tumors. It is directed against the vascular endothelial growth factor receptor 2 (VEGFR2). By binding to VEGFR2 it works as a receptor antagonist blocking the binding of vascular endothelial growth factor (VEGF) to VEGFR2. VEGFR2 is known to mediate the majority of the downstream effects of VEGF in angiogenesis.[4]" wikipedia,
Has been approved by the FDA, oncologist still have a tough time as to when integrate this drug in their cascade of treatment to offer to their patients with these conditions. And this despite the clear failure of the many standard therapy offered first. The average one year survival being given by Gastric cancer current treatment is globally poor since most of the patients affected in our experience are relatively young. And current result of Cisplatin or Oxaliplatin -5-FU based therapy remain repeated endlessly without progess. In france, there is more use of Taxane based treatment, particularly in metastatic cancers. The clear role of this drug, Ramucirumab is currently undefined as it may move from 2nd line (as released by the FDA) and as more clinical trials are moving forward, and also and mainly as oncologists are moving away from standard therapy to target therapy.
In this disease, we are still missing the mark. And results of current treatments impose this glooming conclusion.
The basic understanding is still predominantly that the disease grows from a chronic irritation by gastric acid onto an unprepared squamous epithelium of the Esophagus. This basic idea prompted scientist who eventually won the Noble Process proving that the presence of H.Pylori could induce a neoplastic syndrome. By Chronic Irritation basic genetic understanding would suggest an onslaught on the NF-kB and an intense activity of the epigenetic area where the c-MYC,
RUNX and c-FOS reside. Constant infection or Acid induced irritation means also that some receptors will be desensitized to the point of shutting down of downstream genes which will end up methylated or suppressed or even mutated while some transcription factors (and subsequent miRNA ) will be over expressed. We know this disease to be highly metastatic to the lymph nodes, liver and peritoneum. We know that seeding through the peritoneum with local invasion to the Ovary (Krukenberg) and local invasion to the rest of the GI track (and the dread occlusion of the GI track). But none is of these data has been completely explored fully. And the story of agents acting of the epigenetic zone has not been fully elucidated or tackled!
Even the anti VEGEF, anti EGFR, and anti Her-2 can only act whenever their action reach the epigenetic area....our efforts in this disease can only be significant until the level of c-FOS, the CREB, the cytokines, and effect on Mitochondrial processes are clarified and neatly addressed. How molecular transfer is affected and how we use this information for therapeutic purposes could make the new difference in this disease. The mere fact that the there is a transformation to Barret disease, gives tremendous opportunity to stop the disease or at least to bend these events preventively (what is the MEK doing?).
For the time being, the success of the EOX and other combinations continue to make us believe there is a truth in these statements, and our focus should still be from the blast to a targeted therapy in these cancers...
The CRBCM is still at work...from Warsaw Indiana.
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