The Hedgehog, Ptch1, AND the Gli zinc-finger transcription factors

If there is an example where GENE INTERFERENCE could have a meaningful impact, it is in this pathway like a deluge of gene activations.  The impact could extend from Basal cell to bladder cancers to Gliomas!

"PTCH1 is a member of the patched gene family and is the receptor for sonic hedgehog, a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis. This gene functions as a tumor suppressor. The PTCH1 gene product, is a transmembrane protein that suppresses the release of another protein called smoothened, and when sonic hedgheog binds PTCH1, smoothened is released and signals cell proliferation." wikipedia.

POLIZIO ET AL
 The vertebrate Hedgehog (Hh) pathway has essential functions during development and tissue homeostasis in normal physiology, and its dysregulation is a common theme in cancer. The Hh ligands (Sonic Hh, Indian Hh, and Desert Hh) bind to the receptors Patched1 and Patched2, resulting in inhibition of their repressive effect on Smoothened (Smo). Smo is a seven-transmembrane protein, which was only recently shown to function as a G protein–coupled receptor (GPCR) with specificity toward the heterotrimeric guanine nucleotide-binding protein G_i. In addition to activating G_i, Smo signals through its C-terminal tail to inhibit Suppressor of Fused, resulting in stabilization and activation of the Gli family of transcription factors, which execute a transcriptional response to so-called "canonical Hh signaling."

WHEN YOU TALK ABOUT ZINC-FINGER YOU KNOW YOU ARE TALKING ABOUT HISTONE MODULATION AND DIRECT DNA INTERACTION, ALL OCCURING MOSTLY THE EPIGENETIC ZONE MOSTLY!  THEREFORE THIS COULD EFFECT EVEN THE LEUKEMIAS!
THE CRBCM IS TAKING A CLOSER LOOK!

"Gli regulation by the opposing activities of Fused and Suppressor of Fused

Maximilien Murone^{1,2ET AL!}

Hedgehog (Hh) proteins are secreted factors that control cell proliferation and cell-fate specification¹. Hh signalling is mediated in vertebrates by the Gli zinc-finger transcription factors (Gli1, Gli2 and Gli3) and in Drosophila by the Gli homologue Cubitus interruptus"

OTHER GENES IMPLICATED!

PTCH1 gene

WNT3A

IRF6

GLI

TGF-beta

TrkC: Neurotropin -Receptor

AND THE DANCE OF GENES CONTINUE!

Sons of the Sevenless

SONS OF THE SEVENLESS/Hypothesis for cancer Research

As we move forward here at CRBCM, we are increasingy  fond of one line of molecules;
first because of their name, and because we believe that their inhibitors could be the answer to the resistance
to some of the medications already in our armamentarium, namely Avastin,  Imatinib and Herceptin.  We believe that the Sons of The Sevenless which are regulator molecules switching on RAS would break resistance to Tyrosine Kinase resistance.  Sons of the Sevenless, what a name!  But don't you remember they say: "KILL THE SWITCH" AND DARK WILL COME.   THE SWITCH IS THE SONS OF THE SEVENLESS...BASAL CELL CANCER OF THE BREAST, THE CRBCM IS AFTER YOU...SINCE THE SUGGESTION THAT BASAL CELL CANCER OF THE BREAST IS LIKE OVARIAN CANCER BY ITS GENOME.  MARK MY WORD: KILLING THE SONS OF THE SEVENLESS OR KILLING THE SWITCH IS THE KEY TO TREATMENT.

ADDING TAXANE (or better yet an Anti-Kinesin) AFTER KILLING THE SWITCH (SONS OF THE SEVENLESS) WILL TURN ON THE MITOCHONDRIAL CASPASE BY AN INHERENT REFLEX MECHANISM WHICH WILL BYPASS BCL-2.  THAT'S HOW YOU LEAD TO CANCER CURE!

OH BY THE WAY,  ADDING STELAZINE TO AVASTIN MAY JUST DO THE TRICK FOR RECURRENT BRAIN TUMORS TOO. IT IS AN ANTI-CALMODULIN AFTER ALL!

RESEARCH IS ON AT CRBCM.