为什么癌症药物开发的临床前模型失败

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...