Recent melanoma research has shown that altering drug administration can improve the outcome. Andre Aplin, PhD, associate director for Basic Research and the program leader for Cancer Cell Biology and Signaling (CCBS), and Jessica Teh, PhD, his senior postdoctoral researcher at Jefferson University, conducted research to examine the impact of two FDA-approved targeted agents, MEK and CDK4/6, on human melanomas that have been grafted onto mice. This research was published in Cancer Discovery, and it showed that changing the schedules of drug administration can improve outcomes.
The Study
The two targeted agents used in the research was MEK, typically used in advanced-staged melanoma; and CDK4/6, recently approved for estrogen receptor-positive breast cancer treatment.
The researchers gave the mice that had human melanoma grafted onto them the two different drugs intermittently. They then repeated this method but instead used one of the two drugs continuously and the other intermittently.
After examining what happened from this method and recording their observations, the researchers moved to testing human melanoma tumor samples. The melanoma tumor samples that were tested were also currently undergoing the same targeted therapy treatment.
Conclusions
When studying the mice with human melanoma grafts on them, the researchers found that "When both drugs were given intermittently, tumor growth increased after a one-week drug holiday, and tumors became resistant to the therapy after about eight weeks. However, if one drug was provided continuously while the other given intermittently, the tumors shrank and remained small, no matter which drug was continuous."
Upon further studying these results, it was observed that continuous MEK had consistently smaller tumors, with some even shrinking to undetectable levels. However, continuous CDK4/6 had some toxicity appear that was not observed in other schedules. Thus, a combination of MEK inhibitor given continuously with intermittent CDK4/6 inhibitor was the most effective schedule in mice.1
When testing the samples of human melanoma tumors, it was found that the pathway in mouse models was also found in the human tumors. This suggests that resistance could be blocked in patients with the same drug as in mice.
