Birds of prey kill and regurgitate food to their young. In time they bring back injured animals for offspring to kill and eat on their own. Oncology has these two choices: killing tumor cells outright; or injuring and feeding them to a patient’s immune system.
Here I suggest that, with a high neoplastic cell count and a still healthy immune system, introducing an anti-metabolite of folic acid may work towards stimulating the latter immune response. Such conditions existed in a particular case in 2011 with some success. That success may have been lengthened, had the triweekly, anti-metabolite infusion waited an additional week, to test for this having been from an immune response. With such a response the anti-metabolite might have been suspended still longer preserving the immune system and lengthening its effectiveness. This would promise itself a chemotherapy against which no cancer could evolve towards resistance. With its occasional fresh starts and new immune responses, it would fail, if at all, with the failure of an immune response to rekindle.
I. Apoptosis is a natural, double-fail-safe mechanism.
- When a cell is injured and potentially dangerous to its organism, the apoptosis mechanism should turn (here fail-safe-1) cellular content into a stew of particles: all to be engulfed and digested by a macrophage(s).
- That stew defaces neoplastic cell walls from within (here fail-safe-2), preventing any recognition of its wall and thus any auto-immune reaction, stimulated by the dying cell.
Conclusion: Injuring or otherwise stressing tumors is far more helpful to their proper recognition by an immune system than is damage which would evoke apoptosis.
II. Leukocytes need to both search out intruders and certify them as of common lineage.
- How could a mobile leukocyte be continually touching cells, leading up to recognition of an intruder and the release of antibodies, without risking injury to too many healthy cells. Isn’t it more likely that some leukocytes are able to recognize and differentiate something emitted by a dying cell, hound-dogging that scent trail back to it.
- Primitive certification of an aberrant lineage would have required two separate hits upon its member cells by a single leukocyte: the second hit confirming that the specific aberration was pervasive and hence, that of a lineage. Surely much as pairs of animals have co-evolved, it is from this weak, double-contact leukocyte that the single contacting B and T lymphocytes with their mediation co-evolved towards a more effective fail-safe. That mediation would come to confirm an intruder lineage’s presence, massively arming the messengers and other B and T lymphocytes, (as well as other leukocytes awaiting the confirmation) to spew out antibodies, cytokines and granules.
Conclusions: Cancer patients may be kept alive by inducing the recalcitrant apoptosis, however, were it possible to induce an immune response specific to the anomaly, such would offer a better step towards a real cure. That may happen if a mild irritant were to injure cancer cells while falling short of inducing apoptosis with its cellular wall distortion: all in such numbers and diversity that a pair of lymphocytes might in their lifetime respectively contact the tumor lineage: contact it, that is, in the elaborately evolved sense. Such may even be done by applying the irritant externally to a bioptic mass of tumor, followed by re-introduction.
III. Any effort by an immune system to defend its host from cancerous cells piggybacks on methods which evolved to ward off microbial and viral assaults.
- These well-harried assailants are solitary in the sense that their malfunctions are irrelevant to their lineage. For them, there never has been a need about which the fail-safe mechanism, apoptosis, would have evolved. Without that, the surfaces of these assailants have remained recognizable far deeper into their deterioration than do aberrant human cells, making them easier to recognize and hence to eliminate.
- Although aberrant cells are so because they failed at triggering their own inherent apoptosis (by I. 2.), the mechanism’s presence makes recognition impossible when it finally does go off.
- Infections leave behind memory cells which are able to jump-start a new response, but anomalous cancer cells are unique to a person, and rarely survived by that person. So an evolution towards memory cells would have had little impetus while being discouraged by lethal auto-immune responses. Such evolution seems not to have occurred.
- Or continued chemotherapy may be weakening the immune system so much as to make (3) moot.
Conclusion: With a sufficient number of recognizably aberrant cells of common lineage, the process would cascade towards total elimination; but tumors (or chemotherapy) have offered a sanctuary, unavailable to infectious microorganisms, and with no memory cells, the cascade is too often quenched without sufficient lag time for wrapping up a last remnant. That remnant has revived with its lethal lineage; that is until now.
The Bhatia Lab at MIT is attempting to make tumors more porous by embedding into them golden nano-particles, heating said particles and cauterizing their neighborhoods. This would give both chemotherapy and immunotherapy access to tumor interiors, overcoming in this case the heretofore impossible task of wrapping things up, of curing the patient.
IV. A treatment gently applying an anti-metabolite of folic acid may act much as the aforementioned bird of prey.
- Consider the exosome complex’s ability to reduce poorly written RNA-fragments. Without particular metabolites needed by the exosome, faulty RNA-fragments are left unreduced. The possibilities of RNA distortion are so numerous, as to allow some cancer cells to be left dying, but wonderfully short of their triggering apoptosis. Couldn’t this erratic effect with its multitude of non-apoptosis-inducing, soft touches, with its multitude of dying tumor cells with cellular walls intact, actually attract leukocytes; and finally trigger an immune response.
- One current case of ovarian cancer is familiar to me. With an anti-metabolite of folic acid, her ca-125 levels plummeted surprisingly in what seemed to me more like an immune response than a chemo’s less thorough killing of tumor cells. The results were uncommon but she had been taking immune boosters, AHCC, concentrated coenzyme q-10, Fucoidan, and the controversial Iscador. The initially high ca-125 level indicated an offering up of many, cancer-leukocyte encounters which may not have been available in less successful applications of Pemetrexed (made by Eli Lily). After ten months, the numbers grimly began to rise.
- Anecdotally, someone is having personal success with million-plus Scoville-Heat-Unit peppers. If those peppers are shown also to interfere with the exosome; then in this hypothetical scenario, such may be able to replace the expensive Ely-Lilly product and, not being harmful to the immune system, may be reintroduced with each new cycle as soon as ca-125 numbers begin to rise.
Conclusion: Isn’t it possible that, more often than imagined, immune systems are responding by recognizing and reducing tumors:
- But by the clumping of aberrant cells, and absence of memory cells, they fade short of wrapping things up and, by their partial success, lose the requisite level of aberrant cells needed for a chance rekindling.
- Or rather than halting therapy at the precipitous drop in ca-125, continuation is weakening the immune system beyond its rekindling capacity.
Are such failures mistakenly attributed to adaptations of the neoplastic lineage?
Had her (above) treatment been stopped earlier (it did quickly drop her ca-125 from the 500’s to 37) with similar results and a supported immune system; how tempting it would be to re-introduce it upon her ca-125’s upward return; that is, if it ever had gone back up. Unfortunately she switched to an experimental treatment, and for coherent results, abandoned important naturalistic supports to her immunity. Seven months thereafter, she died.