The present invention relates to a method for treating cancer in a subject by killing tumor initiating cells, inducing differentiation of tumor initiating cells into differentiated cells or blocking the conversion of differentiated tumor cells into tumor initiating cells, which method comprises the step of administering to said subject a therapeutically effective amount of a modulator of the protein tyrosine phosphatase, non-receptor type 11 (PTPN11) gene or of its gene product (Shp2). The present invention also provides a siRNA decreasing or silencing the expression of protein tyrosine phosphatase, non-receptor type 11 (PTPN11) and/or an antibody specifically binding to protein tyrosine phosphatase, non-receptor type 11 (PTPN11), for use as a medicament to treat cancer according to the methods described herein. The present invention also provides a peptide comprising an amino acid sequence specifically recognized by protein tyrosine phosphatase, non-receptor type 11 (PTPN11), for use as a medicament to treat cancer according to the methods described herein above.