Pathogenesis of Neoplastic transformations.

Speculative sources of Neoplastic disease

As we plan Cancer Prevention, it seems logical to target potential mechanisms that likely could initiate the neoplastic process in order to propose logical steps.  And clearly, from a beginner stand of view, and from data screening of various cancer, this task could be daunting.  However major patterns have to be proposed as we examine what works, and what are the main metabolic disturbances in each disease.
*In Kidney cancer for example, Here abnormality in the Von Hippel Lindau gene (gene that promote UBIQUINATION) has supported strongly the involvement of an exaggeration of deficient Hypoxia induced factors (HIF) and related proteins.  This facts lead to the removal of inhibitor forces leading to the expansion of VEGF and PDGF.   It takes blocking the either the the VEGF (Avastin) or blocking the MTOR down the line (Everolimus) to slow down the neoplastic process.   Anything in between may have not been efficient.   Hypoxic conditions often found in patient with obesity (associated with sleep Apnea) may favor the frequency of this disease.   The involvement of VEGF explain the importance of abnormal Angiogenesis in this disease...the tumor is bloody ...Therefore, optimizing Oxygenation (CPAP use in obese patient with sleep Apnea), decreasing or impairing VEGF, could have significant prevention use.   Optimizing Iron level may also have a positive impact should studies initiated here further support that iron deficiency may exacerbate the various cellular metabolites.   Interferon and IL-2 should be consider under this light (as to their effect on the VEGF-MTOR  axe. The involvement of Ubiquination beg the question on whether Velcade and anti-TNF related compound may add to the therapy in Kidney cancer.  One thing is for sure, all cancerous transformation try to escape the immune system, and Pembrolizumab could be discussed further within the contest of this disease!   our knowledge is rapidly expanding.

*In Lung Cancer, the neoplastic transformation is diverse since some non smokers are known to develop the disease.  Here we believe that diet based on high levels of anti-oxidant without sufficient compensatory iron (iron deficiency in women particularly) and HIF gene isoforms may lead to  chronic intoxication triggering once again EGFR/VEGF expansion.   Susceptibility of these cancers to Cetuximab/ERBITUX strongly support this hypothesis. Detoxification may also be influenced by CYP1A1 and GSTM1.

In standard lung cancer however, not only HIF is involved, but there is now increasing suspicion that alterations at the MDM-2 has entered the possibility of initiating the disease process forcing further Ubiquination or intervening at some point, affecting the P53, c-MYC, NPM1 and even prot 14-3-3 ("Phosphorylation of Cdc25C by CDS1 and CHK1 creates a binding site for the 14-3-3 family of phosphoserine binding proteins. Binding of 14-3-3 has little effect on Cdc25C activity, and it is believed that 14-3-3 regulates Cdc25C by sequestering it to the cytoplasm, thereby preventing the interactions with CycB-Cdk1 that are localized to the nucleus at the G2/M transition.[wikipedia) effect on Ubiquitination should be re-emphasized.   With stimulation and amplification of the EGFR/VEGF come the importance of ALK, BRAF, again factors that have enterec lung cancer therapeutics since agents active here have become available (to be continued)