Questions for researchers! Melanoma as an example !

When a cancer continues to rise
-it means it is more environmental?
-It means its central mechanism continue to escape us
-It means the isoforms of the genes causing it,  is more frequently found in the population
-It means that many isoforms can lead to it, again here we need to know the basics?  does the frequency of cancer in society firmly linked to the frequency of the gene Isoforms?
-does the frequency means we keep missing the fundamentals?
-Or does it means the tumor has greater facility to penetrate the neoplastic transformation, or reach easily the "wild genes" or genes of importance in differentiation...
or genes capable of autoregulation?
or genes capable of suppressing other genes
or genes susceptible to Vitamin depletion
The prominence of Vitamin and hormones in society seem to suggest this last point!  Or is it vitamin imbalance?
In Melanoma for example it is established that the disease seems to occur more frequently in patients who burn rather than tan. And that sunburn would more likely be the trigger!  What that tells you about their MCIR gene, their FAK and induction of the Wnt (association with LEF1), and Notch,  Now that we are speaking MITF, and GNAQ/GNA11, or is it a deficiency of the SOCS family gene?
-Association with moles?  Dysplastic moles have up to 80% risk of Melanoma development, particularly when familial tendencies are implicated? what that tells us about what gene is involved is it MITF still?or is it PPP3CA (interferes with dephosphorylation of DNM1L, HSPB1 and SSH1)(will Etoposide helps here?with Cisplatin may be?  When you say this, is it POLR2C, the culprit?
or is it PAX3,MEF2, or Calsarcin-3.
well don't forget insufficiency of p16/CDKN2A when insufficiency of inhibitor of this major pathway relieve the block on cell division...
What gets BRAF so involved Or is it the involvement of Rho/ROCK.  What BRAF has to do with MITF
why inability to cope with change in skin color shuts down apoptosis?  Can interfering with splicing affects
What the hell Xeroderma has to do any how?RAD2, ERCC,DDB2,POLH,XPA,XPB.
Or simply BRAF is locked in Autoregulation, being truly a driver mutation, or relieved of its blocker or ubiquitinating substrate?  Is the PTEN present or not (is it more involved in internal Melanoma-lung?)
what about POU3F2 and PIAS, and miRNA-211, should we block TAF15? (sparing TATA and HSP27?)
can blocking the FGF worth while?
what about the expression of c-Kit (lentigo), where are the DNA repair genes? Should we focus on abilty of this cell to deal with hypoxia? (it seems to enjoy this path?)
There is much to be done, but where are we....
AT CRBCM, we are still at work!