Cancer, the Second Largest Cause of Human Mortality

After cardiovascular disease, cancer is the second most prevalent cause of death in our species. One of the most important parts of a future toolkit of diverse rejuvenation therapies is a robustly effective, low-cost universal cancer therapy, one that can be applied to near all cancers with little need for customization. The best approach to that end is likely some form of interference in telomere lengthening. Unlike other known differences in cancer cells, this is plausibly the one aspect of cancer biochemistry that is both vital and immune to mutational change. A cancer can evolve its way out from under many forms of treatment, but not one that blocks the means by which cells remain able to replicate. Without a way to lengthen telomeres, cells die after a given number of replications, even cancer cells.

As noted in today's open access paper, overall cancer incidence is rising as the number of older people increases. This is an expected consequence of success in raising life expectancy; cancer is an age-related disease. As the immune system declines in effectiveness and forms of damage spread in the body, there is an ever greater chance of cells suffering a combination of mutations and circumstances that leads to cancer. Meanwhile, the individual risk of cancer is declining and odds of survival following a cancer diagnosis are increasing, a consequence of both public health measures and improvements in medical technology.

Mutation and cancer are core features of the biochemistry of multicellular life. Evolution needs mutation, and stem cells require the ability to replicate without limit. Some species are much more resilient to cancer than ours, but cancer will never be entirely eliminated as a possibility given the way in which our biology functions. For so long as the ability for cells to replicate exists, there will be failures of regulation that allow that replication to run amok. Thus it will always be important to have a cost-effective, highly reliable universal cancer therapy. That such a thing does not yet exist imposes a vast cost in suffering, lives, and funds expended on medical treatment.

Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life Years for 29 Cancer Groups From 2010 to 2019

The results of this systematic analysis demonstrate the substantial and growing global burden of cancer, with patterns of burden differing by sociodemographic index (SDI) quintile. In 2019, cancer-related disability-adjusted life years (DALYs) were second only to cardiovascular diseases in their contribution to global disease burden, and in the high SDI quintile, cancer overtook cardiovascular disease to become the leading cause of DALYs. Between 2010 and 2019, the number of new global cancer cases and deaths increased by 26.3% and 20.9%, respectively. However, the largest percentage increases in cancer incidence and mortality during the last decade occurred in the lower SDI quintiles, likely reflecting ongoing epidemiologic transitions, demographic shifts, and disparities in cancer prevention, care, and control.

While the absolute burden of cancer grew from 2010 to 2019, global age-standardized incidence rates remained similar at -1.1% and mortality rates decreased by -5.9%. These age-standardized mortality results suggest cautious optimism that some progress may have been made in early diagnosis and cancer treatment globally during the last decade.

However, inequities in the distribution and growth of cancer burden around the world diminish this potential advancement and suggest that an acceleration of efforts to effectively address cancer burden are needed. Of particular concern, recent progress in reducing age-standardized incidence and mortality rates seems concentrated in higher SDI locations, while both rates are still trending upward in lower SDI locations. The increasing age-standardized incidence and mortality rates in lower SDI quintiles may reflect several factors, including shifting population age structures, increasing capacity for diagnosis and registration of cancer cases and deaths, and changes in cancer risk factors, such as metabolic, behavioral, environmental, and occupational exposures.

Comments

You did an earlier post, regarding Jim Mellon's Juvnescence company, which was going to raise investment funds for the emerging longevity health industry.

They were supposed to launch their IPO last year, but nothing materialised.

Are they still intending to go public?, and if so, does anybody know when?, as they have gone very quiet.

Could we have a blog update?

Posted by: Harry at January 7th, 2022 4:10 PM

Any rough thoughts on how a telomere therapy will work (delivery method etc)?
I've never really heard the details on this, other than "we need to make it impossible for cells to replicate endlessly".

It seems like an approach to train the immune system at being more effective at destroying cancer will be a much easier approach (RNA vaccines?), although as you say... maybe not a great long term solution as cancer will learn to mutate around this.

Posted by: GREGORY S SCHULTE at January 8th, 2022 12:07 PM

@GREGORY S SCHULTE:

If you refer to WILT, I always have heard that the delivery method will be some kind of gene therapy that deletes TERT. Of course, no such wide-coverage, safe gene therapy exists yet in humans, but it's actively researched for other diseases. I think the most difficult part will not be that, though, but the replenishment of stem cells in all tissues of the body. It's much less mature than gene therapy.

Posted by: Antonio at January 8th, 2022 12:51 PM

@Harry

I think after shooting so much of their bank roll on AgeX, which is sliding down the tubes, Juvenescence has gone into reflection mode, as many of these "longevity holding company" models may have bitten off more than they can chew in terms of running a successful portfolio in such a manner

Life Biosciences (David Sinclair's fiefdom) pared back their 9 programs to only 3 now

I suspect we will see the same thing happening at Cambrian with their insane amount of 16 active programs

Posted by: james tabor at January 9th, 2022 8:12 AM

@jimooz: Very interesting! It could be used as a senolytic too!

Posted by: Antonio at January 10th, 2022 3:39 AM

Reason, you state that stem cells require unlimited replication, but to my knowledge outside of embryonic stem cells, no human stem cells actually have this ability. Further, although cancer cells require a way of elongating telomeres, it is not clear that we'd want to reduce telomerase activity as a preventative, given cancers increase exponentially with age, and telomere lengths decline with age. In short, WILT is a very risky proposition.

Posted by: Mark at January 10th, 2022 6:32 AM

suppressing hTERT and telomerase body wide would also suppress immune system. Indiscriminatory suppression of telomerase it's just killing cancer with the host together. Bad solution. So what we need is a delivery system that targets cancer cells only which we don't have. And when we would have it, we have many more toxic components for cancer than telomerase suppressors. Universal indiscriminate cancer therapy using telomerase suppression is impossible. The evolution attempted this and it is now highly effective through SASP at suppressing telomerase at old age, but the only achievement of SAPS telomerase suppression is more cancer and tremendously speeded up aging and (soon) death. The better hope is the agent that promotes telomerase in healthy cells and suppresses it in cancer cells. Such effect was observed with sylibinin and baicalin, which are weak telomerase activators (and in only some tissues), but suppress telomerase in quite a few cancer types. This path to universal cancer cure is indeed promising.

Posted by: SilverSeeker at January 10th, 2022 9:13 AM
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