Historically, most drugs have been identified by high-throughput screening, i.e. you purify an enzyme of interest and test billions of different chemicals against it for the desired effect. You then test for an effect in cell culture (compared to healthy cells), or you can screen directly against the cancer cells. Once you have that evidence, you test whether it has effects in mice, and only after that can you test anything in humans.
It’s possible to propose a single chemical and get it right by chance, but testing a single chemical is cheap. In an already-equipped lab, the initial cell culture data will probably take a few weeks and under a thousand dollars, and after that you will have people willing to help and/or fund you. The lack of even this initial evidence is generally a good reason to believe that something doesn’t work.
With regards to hypotheses, a lot of the early drugs were identified by chance—there’s a description at History of cancer chemotherapy. Most of the current interest is in targeted therapy, i.e. intended to act against specific proteins involved in various types of cancer, and the starting point is the identification of that protein. Chemo drugs are a bit different since they’re a very broad class (they target rapidly dividing cells in general, which is also what causes the toxicity), and the metabolic networks they affect are generally well-known, so the initial hypotheses tend to be about new ways that you can intervene in those networks. There are other approaches to the various steps as well, e.g. structure-based drug design has had some success, but not yet enough to replace the screens.
Historically, most drugs have been identified by high-throughput screening, i.e. you purify an enzyme of interest and test billions of different chemicals against it for the desired effect. You then test for an effect in cell culture (compared to healthy cells), or you can screen directly against the cancer cells. Once you have that evidence, you test whether it has effects in mice, and only after that can you test anything in humans.
It’s possible to propose a single chemical and get it right by chance, but testing a single chemical is cheap. In an already-equipped lab, the initial cell culture data will probably take a few weeks and under a thousand dollars, and after that you will have people willing to help and/or fund you. The lack of even this initial evidence is generally a good reason to believe that something doesn’t work.
With regards to hypotheses, a lot of the early drugs were identified by chance—there’s a description at History of cancer chemotherapy. Most of the current interest is in targeted therapy, i.e. intended to act against specific proteins involved in various types of cancer, and the starting point is the identification of that protein. Chemo drugs are a bit different since they’re a very broad class (they target rapidly dividing cells in general, which is also what causes the toxicity), and the metabolic networks they affect are generally well-known, so the initial hypotheses tend to be about new ways that you can intervene in those networks. There are other approaches to the various steps as well, e.g. structure-based drug design has had some success, but not yet enough to replace the screens.