We herein suggest that ATRA or selective RAR-β agonists with improved toxicity profile, or potentially compounds that block actomyosin tension, can open new avenues in the treatment of PDAC by biomechanically reprograming PSCs to a quiescent-like state, and restoring the biomechanical homoeostasis of the microenvironment to inhibit cancer invasion and progression. This evidence concerns the gene RARB and cancer.