Thanks for sharing a great article. Overall, I think the path to develop a drug is very multi-dimensional, cost and time intensive and very slow. Some other elements to add to the article:
- The preclinical drug discovery phase was not mentioned much. This phase involves discovering/designing/creating an actual drug against a potential biological mechanism/target uncovered by biology/genomics. Although this is generally seen as a more tractable element of the drug development path, it can still be very difficult and requires many years of additional research. Even so, some targets are well known to have great potential in disease, but it has been very difficult to generate a selective and potent drug against it. This phase typically does involve more "theoretically defined" research (although it is still messy) with chemists, biophysicists and pharmacologists, which fit more into the article's mention of the "mathematician". Yet, in line with the article, these often-talented people cannot always create a suitable drug for a given target. Providing further evidence that it is not "just" a lack of mathematically talented individuals.
- The reasons for drug failures in the clinic can be more numerous than alluded to in the article. Some drugs are very toxic, not only because of off-target side effects, but potentially also due to on-target side effects. In deadly cancers, this might not be so much of a problem, but it can still be a limiting element when we combine drugs to limit the surfacing of drug resistant cancer cells.
- As mentioned by others, cancer cells are cells from our own body, and they utilize our body's functions in excessive or highly altered manners to grow. However, blocking these functions selectively in cancer cells can be difficult (especially if non-genetically) as these functions often are still present in all other cells.
- Cancer metastasizes, cancer cells can spread across the body and generate new tumors elsewhere in the body. This can be almost anywhere, and it can be very difficult to detect early metastases in a patient. Hence, stopping treatment too early, even though the doctors might not see any cancer cells and the treatment has strong side effects, means you could redevelop cancer. Moreover, some metastatic sites might be in locations that are hard to reach for a given drug, hence they might not be fully targeted by a given drug.
- Full-blown cancers typically do not develop solely because of a single driving genetic alteration. Instead, a series of 2~5 genetic/biological alterations from a potential pool of dozens of genetic factors in combination leads to an aggressive tumor. Note though that it can be true that a single genetic alteration is dominant and drives a large part of cancer growth. Even in a single cancer type (e.g. colon cancer) the combination of 2-5 alterations leading to aggressive cancer can be different. Moreover, even within a single patient, different metastatic sites might evolve on their own and acquire different combinations of these driving factors. Hence, to truly treat some cancers targeting multiple drivers would be ideal, and each patient might require a relatively unique approach.
- Cancer cells are genetically unstable and can rapidly alter their genetic makeup. The DNA of normal human cells consists of two sets of 23 chromosomes that are well-organized and add up to ~3 billion DNA base pairs (the code of life). Cancers show very variable chromosome numbers and some advanced cancers can have more than 100 chromosomes. Moreover, cancer chromosomes can be heavily altered, where pieces of other chromosomes integrate into others, translocate, bridge, reconnect. It can be a total soup of >10 billion DNA base pairs. Moreover, these changes are different for each cancer, so every cancer patient will be more or less unique. This genetic instability also allows cancer cells to rapidly mutate and adapt/develop resistance to a given drug treatment.