Abstract: Embodiments of the instant disclosure relate to novel methods and compositions for treating tumors resistant to platinum-based chemotherapy. In certain embodiments, methods of treating tumors herein can include administering an effective amount of at least one M1 aminopeptidase inhibitor in combination with at least one platinum-based chemotherapeutic agent separately or in a combination therapy. In some embodiments, methods of treating tumors disclosed herein can include screening and/or selecting a subject suitable for treatment based on NPEPPS gene or protein expression in the tumor to be treated. In other embodiments, methods of treating tumors can include administering a composition including a combination of at least one M1 aminopeptidase inhibitor and at least one platinum-based chemotherapeutic agent. In certain embodiments, compositions disclosed herein can include at least tosedostat and carboplatin.