Accumulating the Groundwork for the Ultimate Cure for Cancer

It's good to be living at a time in which we can seriously discuss in some detail exactly how an ultimate cure for cancer would in fact be built: what biotechnologies are needed, how our biology would have to be changed. While we might all wish our births to have slid at least a few decades into the future to benefit from what will come, being here now puts us in a far better position than that of our immediate ancestors. Personally, I'd settle for the greatly improved odds of survival imparted by a very robust suite of cancer cures - and that is exactly what will emerge with the next generation of targeted cancer therapies that use some combination of immunotherapy and nanoscale engineering. Cancer doesn't worry me anywhere near as much as other aspects of aging, given the way the odds look to be shaping up. If you're two to three decades away from the prime years for cancer, then you should probably feel the same way.

In any case, one of the longer term research projects that is a part of the Strategies for Engineered Negligible Senescence (SENS) is the technical basis for what might be described as the ultimate cure for cancer. It goes by WILT, or Whole-body Interdiction of Lengthening of Telomeres. The short version of the idea is to turn off the ability of the human body to do the one thing that all cancers depend upon, which is lengthening telomeres beyond their normal limits. Telomeres are the protective caps at the end of chromosomes that progressively shorten with each cell division: one of their functions is to prevent runaway division of cells (i.e. cancer), but that roadblock can be evaded by a cancer that evolves any one of a number of ways to abuse mechanisms that the body normally uses to repair and lengthen telomeres in the few cell populations that need it.

The not inconsiderable downside of WILT is that a person who has undergone this treatment will have a reduced life span without access to procedures for regularly replacing their entire stem cell populations - turning off telomere lengthening will kill the possibility of cancer, but also put a short timer on the stem cells that need that process in order to keep repairing the body and replenishing cells. To my eyes this seems like an unnecessary risk when balanced against the future robustness of cancer therapies under development - but it's hard to argue against WILT as an ultimate cancer therapy.

That is, provided all of the scientific assumptions about WILT are correct. For example, that we know all of the biological processes by which telomeres can be lengthened, and that shutting them all down doesn't cause any other harm beyond the loss of stem cell longevity. So there is a certain amount of groundwork to be done to seal the case for WILT as ultimate-cancer-therapy-with-big-but-possibly-acceptable-downside, and the SENS Foundation has been funding some of it, whilst keeping an eye on other related research already ongoing. Here is an outline of one recent advance in knowledge:

To develop an unbreachable defense against cancer, SENS Foundation is pursuing the WILT (Wholebody Interdiction of Lengthening of Telomeres, or OncoSENS) strategy of preemptively deleting genes essential to the cellular telomere-maintenance mechanisms (TMM) from all somatic cells ... The strongest challenge to this approach, granting the periodic replenishment of somatic stem-cell pools with autologous but OncoSENS-ready stem cells, has been the possible existence of functions of TERT (telomerase reverse transcriptase - the catalytic subunit of telomerase), other than the lengthening of telomeres itself.


A careful test of the development of [mice engineered to lack TERT] would be expected to provide strong evidence on the subject one way or the other, provided that telomere lengths did not shorten excessively. Nobel laureate Dr. Carol W. Greider, whose career in telomerase research and path to the Nobel prize began when she first identified the enzyme in 1984, has finally carried out such a test, and she and her collaborators have generated results that strongly support the safety of this element of WILT.


This little-heralded, meticulous investigation into the effects of ablation of the telomerase catalytic subunit in mice with human-like telomeres provides us with strong reassurance that, should it prove to be the preferred approach for implementing the OncoSENS strategy, the effects of knocking out TERT would be limited to those dictated by the loss of telomere-lengthening per se, and would not lead to an unintentional loss of some essential but hitherto-unknown physiological function.

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