Proposing a Solution to the Wrong Problem in Cancer Research

Despite rapid progress in biotechnology, cancer research is an expensive and slow-moving field when it comes to results in the clinic. Many projects that absorb years in time and millions in funding produce failures or only marginal successes, little better than presently available options. Therapies developed at great cost are in any case usually only applicable to one out of the thousands of varieties and subcategories of cancer. The oppressive regulatory environment for medicine in the US serves to make these issues far worse and more costly than they might be, but the underlying nature of the field is present in all regulatory regimes. All of this makes cancer research a comparatively unattractive option to for-profit biotechnology investors, and that is a significant problem. These investors are a vital part of the machinery of the marketplace, and the funds they provide are needed to in order to start companies that work to move new medical technology from the laboratory to the clinic.

Here, some of the researchers in our longevity science community propose a financial solution to this problem, a way to better distribute risk in for-profit medical development investment so as to encourage greater participation. It is certainly true that at the present time, due to the increasingly unwise actions of those who control the monetary systems of the developed world, there is an awful lot of money sloshing around in search of returns. Even small improvements to the risk profile of biotechnology investment at the high end could pull in greater funding for the industry by ranking it more attractively in comparison to other options - and there is a growing dearth of other options for managers sitting on hundred of millions or billions or more.

Cancer megafunds with in silico and in vitro validation: Accelerating cancer drug discovery via financial engineering without financial crisis

Biomedicine faces a dilemma. Despite many recent scientific breakthroughs demonstrating a clear potential for combating cancer, there has been no significant private investment in cancer drug research and development. Both constantly rising costs and increasing rates of failures in the late stages of clinical trials have made the pharmaceutical research and development unappetizingly risky from a financial perspective.

In particular, there are two main challenges. First, on average the success rate of clinical trials is low so that the average financial yield is low. Second, the large investments required to bring a single treatment to the market lead to an all-or-nothing result: the risk is high. To increase funding for cancer research while providing adequate financial returns to investors with wide ranging risk profiles by investing in multiple clinical trials at once thereby mutualizing investments and diluting risks, the concept of a "cancer megafund" was proposed. A massive amount of investment capital would support a portfolio of many drug development projects in order to spread the risks associated with any stand-alone biomedical project. The resulting lowered default probabilities could make returns attractive to investors. By issuing Research-backed Obligations (RBOs), it could be also possible to attract both fixed-income and equity investors.

The authors go on to present options for a cancer megafund and run the mathematics to demonstrate likely outcomes. They make some suggestions as to where a few of the problems of agency and accountability lie in the matter of assembling and managing large-scale funds, and how to approve governance so as to minimize those problems. All good insofar as it goes, but I can't help but feel that this proposes a solution to entirely the wrong problem. The problem is not risk management, the problem is that most cancer research as currently conducted by the mainstream is not delivering meaningful advances at a feasible cost. If problems are to be solved, then that is the one to be solved.

I have long said that true progress in cancer research will come from greatly expanding the range of cancers that can be treated with a given technology platform. An alternative way of looking at that is to say that true progress requires crushing down the cost of delivering an advance in the capabilities of medicine for each different type of cancer. At the moment most cancer research is very specific to one subtype of cancer, and there is no reasonable expectation that the technology used can be adapted to any other cancer. This is especially true of small molecule approaches, traditional drug discovery and development, and so on. This approach to cancer isn't producing results that are sufficiently good to pull in investors like a magnet, given current costs and risks.

There is a linked set of figures to consider here: cost of development per therapy, the number of cancer types that therapy can address, the risk of failure at the end of development, and the cost to adapt the underlying technology platform to another cancer type. Right now all of those numbers are pretty terrible for most cancer research. Pulling in more funding won't change that fact, and may just serve to let the present mainstream of the research community continue along with business as usual, as carried out for cancer research over the past couple of decades. I'm personally of the opinion that a funding crunch is probably good for the community so long as it spurs a change in research strategy, given that there are a number of possible technological options to improve some of the numbers above.

The approach I favor for the mid-term future of cancer research, beyond the coming next generation of therapies largely based on immunotherapy, is some form of temporary blockade of telomere lengthening, possibly global, possibly targeted, informed by the SENS Research Foundation outline for this class of technology. Telomeres cap the ends of chromosomes, a part of the mechanism that limits the number of times a cell can divide. Telomeres lose length with each cell division, and when they become too short the cell destroys itself or becomes senescent and ceases replication. All cancers have to abuse telomere lengthening in order to grow, and there are a limited number of mechanisms responsible for that lengthening: telomerase expression and the alternative lengthening of telomeres (ALT) processes. Turn them all off, and that is that for any cancer. Not all that many research groups are working on this front at the moment, but the work that has been accomplished is promising. The prospect of deploying a truly universal cancer treatment platform for much the same cost as a single therapy for a single type of cancer, as research proceeds in the mainstream today, is very attractive. It merits a far greater level of investment than presently exists.


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