Cancer where are we now in 2020 , what does MPL do !

Thanks @ Peteepoo and Captain Goodvybes good question.

At any point of time 14 million people across the world are dealing with Cancer.

There is approximately 100 different types of Cancer.

Cancer arises as normal cells mutate and sometimes the immune system eliminates them, causing them to self destruct in their infancy.

Some mutated Cancer cells mutate more and metastasised to other parts of the body and colonise new Cancer cells in a new location.

Cancer as we know can have multiple mutations whereby anti Cancer therapies can kill some of them or all of them. But one Cancerous stem cell can mutate and populate a new cluster.

Another problem is sub clones of Cancer such as Glioblastoma, which can have 6 different sub clones. Thus we can eliminate 5 as an example but not the 6th.

Another problem is Cancer cells connect with healthy cells giving blood flow and removing waste products. In some cases the Cancer cells deceive the immune system to think that they are healthy cells. Cancers cells are a master of adaptation.

Some Cancers cells change gene expression when treated with radiotherapy or chemotherapy

Treatment can be surgical, radiotherapy, hormonal or immunotherapy, but treatment is not 100% effective 100% of the time.

So where does Monepantel ( Amino-Acetonitrile ) work in the body system.
This is where it gets very technical.

We all know it inhibits mTOR. mTOR is a bio positive and negative feedback system. It’s like a back up system when things go wrong. But, Cancer cells can deceive this system. It is thought, that the negative bio feedback system then eliminates the Cancer . There are only so many Cancers that can be manipulated by mTOR inhibitors, it is not a silver bullet for all. Some Cancers have a shield called fibroblasts ( imagine a fibreglass umbrella over lapping the cancer cells ) Some drugs called Focal Kinase Inhibitors can potentially target this fibreglass matting then allow “ conventional “ treatments like MPL to eliminate the cell colony.

Ok, onto the hard to understand scientific jargon on why MPL works. I will explain succinctly but not in detail, as I would be typing a war and peace.

1. mTOR inhibition causes cell homeostasis (equilibrium) , it increases antigens and viability ( bodies Cancer cell fighters )
it increases memory T cells ( specialised mutant fighting cells ).

2. mTOR inhibition causes reduced (S6k1) a gene which is amplified in some Cancers . It reduces ( e1F4e) another gene amplified in some Cancers. It increases ( 4E-BP1) a tumour suppressive gene.
all three combine to promote protein synthesis , cell growth , metabolism of good cells , but controls autophagy ( removal of mutant cells).

3. mTOR inhibition reduces ( c-Myc ) cells , these cells are over expressed in Cancer causing more proliferation.

4. mTOR inhibition interferes with the Cancer cell cycle division. It affects regulatory proteins to the Cancer cell ( being cdk2 /cdk4/Cycline E and A)

5. The Cancer cell requires four stages to replicate G1/G2/M and Go. MPL interferes with the expression of cell cycle regulatory proteins. MPL stops proteins from entering Stage G2 , thus depriving the Cancer it’s DNA replication.

Ok , so does MPL causing an inhibition of mTOR have a downside. Yes, see below.

1. mTOR inhibition reduces amino acid catabolism ( our cohort Cancer trial dogs had some effects of elevated liver enzymes )

2. mTOR impairs the function of Tfh cells. ( immunity helping cells ) so possibly expect enlarged lymph nodes when patients are taking MPL. The assumption is that if Tfh cells are inhibited the body will produce increase B cells ( increased lymphocytes ) increasing the bodies immune defence.

There you have how it theoretically works in Cancer.

In Covid-19 it works a tad differently , in simplicity it works on ion channels functionality ( G2 cell DNA replication phase )