Significance:We report that cell lines of rhabdomyosarcoma (RMS) and cancer cell lines of skin, breast, lung, and cervix are highly sensitive to mTORC1/2 dual inhibitors. mTORC1/2 complexes regulate protein synthesis, cell proliferation, growth, stress responses and survival. The cancer cells died by a catastrophic process, called macropinocytosis, in which numerous single-membrane vacuoles filled with watery fluid formed, merged, and ruptured, killing the cells. Consistent with the findings in cultured cells, the growth of RMS cells implanted in immunocompromised mice was significantly reduced, especially in combination with cyclophosphamide, a standard chemotherapeutic drug to treat RMS.