6) Case Study: Cancer Drugs
DNA-damaging agents have a long history of use in cancer chemotherapy. The full extent of their cellular mechanisms, which is essential to balance efficacy and toxicity, is often unclear. In addition, the use of many anticancer drugs is limited by dose-limiting toxicities as well as the development of drug resistance. Novel anticancer compounds are continually being developed in the hopes of addressing these limitations; however, it is essential to be able to evaluate these compounds for their mechanisms of action.
a. One example of a DNA-damaging agent that interferes with DNA synthesis is aphidicolin. Knowing that it interferes with DNA synthesis, propose three hypotheses of how this agent might accomplish this (think about potential targets and mechanisms you have learned about in the cell).
b. Another set of DNA-damaging agents are alkylating agents, which either cross-link (create covalent bonds) between DNA and proteins or between DNA bases on the same or opposite strands. Hypothesize how these agents might specifically interfere with replication. Offer three different potential modes of action.
c. Clearly DNA replication is important for almost all the healthy cells in our body. How do these DNA-damaging agents manage not to kill the patient?
6) Case Study: Cancer Drugs
DNA-damaging agents have a long history of use in cancer chemotherapy. The full extent of their cellular mechanisms, which is essential to balance efficacy and toxicity, is often unclear. In addition, the use of many anticancer drugs is limited by dose-limiting toxicities as well as the development of drug resistance. Novel anticancer compounds are continually being developed in the hopes of addressing these limitations; however, it is essential to be able to evaluate these compounds for their mechanisms of action.
a. One example of a DNA-damaging agent that interferes with DNA synthesis is aphidicolin. Knowing that it interferes with DNA synthesis, propose three hypotheses of how this agent might accomplish this (think about potential targets and mechanisms you have learned about in the cell).
b. Another set of DNA-damaging agents are alkylating agents, which either cross-link (create covalent bonds) between DNA and proteins or between DNA bases on the same or opposite strands. Hypothesize how these agents might specifically interfere with replication. Offer three different potential modes of action.
c. Clearly DNA replication is important for almost all the healthy cells in our body. How do these DNA-damaging agents manage not to kill the patient?
