Table2.

Challenges faced in current clinical trials assessing targeted anticancer agents and proposed mechanisms to circumvent them

Challenge	Potential solution
Coupling of molecular aberrations to targeted agents	Preclinical cancer research findings indicating potential therapeutic opportunities
Selection of specific mutations based on their predicted functional output	"All-comers" approach or evaluation of functional output of aberrations through functional experiments and/or bioinformatic tools
Subclonality of molecular aberrations	"All-comers" approach and retrospective look or arbitrary selection of threshold
Lack of "actionable" aberrations	Therapeutic agents that do not rely on molecular aberrations, e.g. chemotherapy
Concurring "actionable" aberrations	Second randomization or prioritization based on allelic frequency or prioritization based on frequency of aberration or physician's choice or algorithm combining the above