Triplet joint therapy of Ribociclib with exemestane and Everolimus (mTOR inhibitor), or Letrozole and Alpelisib (PI3Ka-selective inhibitor) were investigated in HR+ ABC patients whose tumor cells endured PI3K/AKT/mTOR and/or cyclin D-CDK4/6-p16-Rb pathway alterations39-41. The gene discussed is RB1; the disease is neoplasm.