The involvement of Rac in the development of therapy resistance was demonstrated as well (Kazanietz and Caloca 2017; Sun et al. 2021; Goel et al. 2016), as constitutively active Rac1 promotes resistance to anti-estrogens (ER) in therapeutic approaches for estrogen receptor–positive (ERþ) breast cancer patients, and has been associated with the acquired resistance to trastuzumab, used for ErbB2/HER2-positive breast cancer patients (Sun et al. 2021). The gene discussed is ESR1; the disease is breast cancer.