Abstract: The present disclosure provides methods and composition for treating multi-drug resistant cancers, in particular, breast cancers, via administration to a subject the composition including a peptide having a sequence complementary to a highly conserved motif present in substantially all integrins responsible for an integrin-mediated attachment-independent chemoresistance to one or more chemotherapeutic agents. The binding of the sequence of the peptide to the highly conserved motif will enhance accumulation of the chemotherapeutic agents in the tumor-initiating cells and in turn restores the function of the chemotherapeutic agents in the tumor-initiating cells.