In conclusion, we demonstrate that PPP1R1A is an ES specific cell cycle modulator which promotes cell cycle progression from G1 to S phase by negatively regulating cell cycle inhibitors p21Cip1 and p27Kip1 and promoting normal transcription of replication-dependent histone genes and that the combinatorial inhibition of PPP1R1A pathway with an IGF-1R inhibitor has synergistic/additive effects on ES cell and tumor growth and dissemination. The gene discussed is CDKN1A; the disease is neoplasm.