Summertime is full of walkathons for cancer. There is absolutely nothing wrong with raising money to help cure disease. But is this money well spent and have we made much progress toward cures? Although many view cancer as an evil monolith, cancer is not a single disease. A glioblastoma took my father’s life roughly 18 years ago this week and yet the prognosis for a patient with glioblastoma today is virtually as awful as it was 18 years ago. Even now, most solid tumors are treated with a regimen of chemotherapeutic agents, surgery and radiation similar to what my father received. Rates of remission move incrementally, if at all, over time. Although we have made some strides, real progress in addressing cancer’s ravages for many indications has been frighteningly slow. Why is this so with the billions and billions raised annually for cancer and deployed in research for cures by governments, universities and pharmaceutical, biotechnology and medical device companies?
There are several structural problems that have led to egregious wastes of time and money and relatively little progress against most cancers. First, I believe the typical research approach to creating new anti-cancer drugs is simply ineffective. Find a marker for a type or sub-type of disease and then find agents that attack cells with that marker. For the most part, with a few exceptions, we haven’t made much progress using this approach and haven’t extended lives for years or decades by doing so. Second, our US regulatory system (FDA) is ill equipped (perhaps also institutionally incapable) to reorganize itself to handle new approaches to curing cancer that have a much better chance of long term success. It still takes forever and costs $180 to $231 million to bring a drug to market. Ridiculous. And third, many companies in the industry are organized and optimized for regulatory and marketing operations that do not correspond well with new approaches that may indeed work. Such organizations are incentivized to create one size fits all solutions. Moreover, they are motivated not to cure anything, but rather to treat diseases (including cancer) as chronic conditions.
Biological systems are very complex, very sneaky and redundant. They are created by Darwinian trial and error and the fittest are the ones that can withstand a multitude of environmental blows that can be thrown at them. So when something goes awry with a cell (such as cancer), it is not typically because one protein is present or missing. Biological systems must compensate for the odd problem or else they do not survive ruthless Darwinism; it is usually attacks from multiple sources that beat their repair defenses. It is the breakdown of the entire system (interplay of genetics and environment/nature and nurture) that enables cancerous growth. It is the rare exception (such as Huntington’s Disease) where one can point to a single nucleotide polymorphism that is responsible for a particular disease state. Because they are all interdependent, one cannot typically analyze individual components in a biological system in isolation. Disease occurs because the system as a whole breaks down not usually because one individual part was the “cause.”
With the above statements, I do not mean to denigrate Roche’s Herceptin or Genentech’s Gleevec which are effective for the populations they serve. See also Pfizer’s Crizotinib and Roche’s Vemurafenib. But we will probably discover that these drugs will be most efficacious when used in combination therapies that address multiple attacks on entire systems. Most diseases, however, e.g. metabolic disorders, cardiovascular disease, and yes, most cancers have a plethora of pathways to march down to progress to disease. The way to solve and knock out the various progression pathways simultaneously and arrest tumor formation is to use systems approaches. Such methodologies require vast amounts of patient data over populations and tremendous amounts of computing power to capture the information in databases and then parse and analyze it.
I believe treatments of the future will usually require a series of diagnostic tests to determine which regimen combination of drugs will be necessary for the sub-type of cancer that the patient possesses. Blood protein assays for these types of diagnostics will require the next generation of micro-fluidic chips from companies such as our portfolio company, Fluidigm. The problem is that the markets for each of the individual tests and drugs will probably not be large enough to recover the costs necessary to invest in developing them under our current regulatory system. Thus, to get where we need to go in the future to create more individualized and effective cancer therapies, FDA will need to undergo a dramatic transformation. Nevertheless, even if the regulatory system were to adapt, the current research and development arms and marketing divisions within drug companies are not structured to be able to address micro-diagnostic markets with corresponding therapeutics. And healthcare providers have little incentive to change methods of hacking out tumors through surgery. Future treatments may involve more elegant solutions such as “signalling nanoparticles” that would function like notification proteins and mark locations where cancer cells exist and further action was required. “Receiving nanoparticles” might then be recruited to cancer sites like platelets, but instead of staunching a wound they would deliver anti-tumor drugs. Without an economic incentive, however, it will be hard to change behavior and get providers to adopt new techniques.
With all of these factors stacked against real change, I guess I should not be surprised that so little progress has been made since my father passed away 18 years ago. Scientists such as Dr. Leroy Hood, Dr. Sangeeta Bhatia and Dr. Geoffrey von Maltzahn have made great discoveries, but without more research dollars being directed appropriately, serious FDA regulatory reform and a complete rethinking of pharmaceutical and healthcare company business plans, I fear that we will be in much the same place in the war on cancers 18 years from now. That is a lot of walkathons for little progress.
