Bless!

In a recent digest, Cedric discussed the problem of tumour lysis. Tumour lysis occurs, when cancer cells die in the toxic and highly inflammatory cell death mode of necrosis, which in severe cases can lead to multiple organ failure and death of the patient.¹

It goes without saying, that tumour lysis must thus be prevented, lest treatment trying to heal the patient inadvertently kill them.

Today, I want to talk a bit about why tumour lysis doesn't happen in all cancers and about what we can learn from this about the prospect of stopping cancer cells from necrotising by shifting their death mode toward apoptosis instead. Those are all big words, but don't worry, I'll break them down as they become relevant to the topic at hand, for knowledge is only ever transformative, if it can be transferred from one mind to another.

Why Tumour Lysis Doesn't Occur in All Cancers

Tumour lysis is a process of uncontrolled cancer cell death, where the cells in question buckle under stressors, to which they for some reason can't respond appropriately. There are two primary requisites for tumour lysis to occur:

1. The cancer cell must be under lethal duress.
2. The cancer cell must be incapable of initiating apoptosis, in response to this duress.

This is also why tumour lysis doesn't occur in all cancer and all patients – in fact, it most often occurs in haematological cancers.¹ Firstly, tumour lysis needs an effective treatment for the cancer at hand, which most patients are sadly left without. Secondly, the treatment must be applied to a cancer cell, which can't initiate apoptosis.

Apoptosis is an orderly process of sacrificial cell suicide, which healthy cells will so routinely engage in, that about half of all neuronal cells generated during embryogenesis (development of an embryo) apoptose.^2–3 During apoptosis, the self-sacrificial cell will digest its own internal components and package them into neat membrane-bound droplets, which macrophages may take up and transport off without much effect upon the surrounding tissue. Apoptosis is generally good and not worrisome.

Now, cancer cells unable to initiate apoptosis still must die, when under lethal duress, as that is the very definition of lethal duress. As they are unable to digest and package their contents in an orderly fashion, they instead die in a lytic cell death, where the cell membrane ruptures and its contents spill out into the extracellular space.³ The prototypical consequence of lytic cell death is necrosis, and the spillage it causes is toxic and highly inflammatory.

In a starkly simplified way you may think about apoptosis and necrosis in the following way:

1. As a cell comes under duress, it will first try to ameliorate the source of this duress.
2. If it can't do this and can't rescue itself, it will go into apoptosis.
3. If it can't go into apoptosis for one of a countless possible reasons, it will survive the duress until it becomes unsurvivable and will then die not of an orderly suicide, but of a violent, disordered death, resulting in necrosis and the toxicity to the surrounding tissue.

When this happens en masse amongst the cells of one or multiple large masses of cancerous tumours, because treatment is sufficiently lethal to these cells, the resultant ailment of the patient is then called tumour lysis syndrome (TLS), which can be lethal to the patient.

What We Can Learn From This

TLS occurs primarily due to some form of apoptotic incompetence, which prevents orderly sacrificial suicide of the affected cancer cells prior to acute lethality of the treatment. This also means, that hypothetically TLS could be prevented by restoring apoptotic competence to these cancer cells.

Now, obviously restoring such apoptotic competence to cancer cells expert at not dying is quite difficult. At this point, we're attempting to formulate such a regimen in order to suppress tumour lysis in one patient without having to stop killing cancer cells. After all, we'd very much like to kill all of them, just by different means. If this regimen turns out successful, we'll naturally add it to the upcoming written guide on the Mosaic Method, described in more detail there, and in a separate digest and/or report.

The very fact, that some cancer cells are susceptible to apoptosis and will rather die normally than necrotise to me seems an indication, that it's theoretically possible to modulate signalling pathways also in apoptosis-resistant cancers to allow them to kill themselves in an orderly fashion. Whether this is true, remains to be seen, but not today.

Next week, I'll go over some of the evidence we have in literature for the feasibility of using therapeutics to achieve a shift from tumour lysis to orderly apoptotic cessation of the cancer cell.

Until then, I hope this has been informative and interesting.

God bless,
Merlin L. Marquard