One of the clinical approaches to increase the duration of disease control has been to identify new agents with a non-overlapping mechanism of action and demonstrated single-agent antitumor activity to combine with platinum and paclitaxel.
The additive analgesic effects of acetaminophen and COX inhibitors, as observed in several clinical trials [2], may also reflect non-overlapping mechanisms of action.
Combining targeted agents that have non-overlapping mechanisms of action with chemotherapy may potentially increase the disease-free interval.
Recent efforts have focused on identifying novel combinations of anticancer agents with non-overlapping mechanisms of action to obtain enhanced anticancer efficacy and reduced toxicity.
There remains an urgent need to enhance the activity of chemotherapy through combinations with biologically targeted drugs that may help overcome resistance and/or have non-overlapping mechanisms of action and side effects.
In contrast, mutation of rsks- 1 together with daf- 2 results in a strain that far outlives either of the single mutations (Chen et al. 2013) suggesting non-overlapping mechanisms of action.
These studies were undertaken because primary and acquired resistance to both agents could be overcome, their partly non-overlapping mechanisms of action, and the well-characterized synergistic interaction between them could be expected in patients with HER2+ breast cancer.
Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising.
Contingent on the premise that the combined agents have non-overlapping and synergistic mechanisms of actions, immediate and effective targeting of tumors with multiple agents appears a successful strategy to improve the clinical outcome of MM therapy.
Furthermore, we applied principles of Hierarchical Information Integration by identifying six separate research engagement actions (e.g., searching, appraising, generating research), identifying the key, non-overlapping subactions of each research engagement action, and undertaking a separate choice experiment for each action [ 61, 62].
Gemcitabine is an interesting candidate for a three-drug combination because of its different mechanism of action and non-overlapping toxicity with respect to the other two drugs.
