Monday, May 13, 2013

NO DEED GOES UNPUNISHED, THE STORY OF SECONDARY CANCER, WE JUST HAVE TO BRACE FOR IT!

As we are being increasingly successful at treating cancers, we are being faced with the decision of how long to keep a patient on treatment and maintenance therapy is increasingly pushed. In some surveys, 70 to 80% of oncologists are treating patients "until disease progression" and that could be a year or even several years".  The truth is that on a cellular level this is a prolongation of stress and sooner or later something is "gonna break".  It is of interest that at the cellular level, that treatment of Hematologic malignancy leads to solid tumors.  It goes to show that heterogeneity of genetic material or variation of genes within the same family is exposed to the same stress as imposed by treatments and yields a various effect on a different lineage of cells. Meaning that the suppression of A molecule could affect A2 of the same family, but with a different outcome.

It is clear that prolonged suppression of non intended genes, is the reason for secondary tumors.  In some cases, new altered genes are caused by the fragility or susceptibility of the host genome!  The point is though, now that we have a secondary cancer with the specific cause, do we look to treat the same as the de-novo cancers?  Do we go to the NCCN standard of care, or do we need to aim at the target mutation caused by our previous treatment?  Empirically, we suggest that a target therapy would be more efficient, secondary tumors call for a different approach since we have more specific information as to the cause.  But a new clinical trial needs to be designed to answer this question!

Secondary tumors happen:
1. When new receptors are completely, irreversibly compromised by our treatment
2. When an related or unrelated gene is is either over-expressed or suppressed (i.e suppression of PTEN) by the treatment.
3. When a bypass activation of collateral gene exists and involves a major pathway (i.e Wnt or Notch pathway by-standing there in the neighborhood!)
4. Some combinations of drugs seem to be prone to causing these secondary tumors (alkylating agents and immunomodulators in myeloma treatment!)

SECONDARY TUMOR IS WAY DIFFERENT FOR DE-NOVO TUMOR!  LET'S FACE IT AND BRACE FOR IT! 
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