Synthetic peptides containing an ankyrin repeat-like motif or portion thereof and mimetics thereof which interact with synuclein-gamma (SNCG) and reduce SNCG-mediated resistance of SNCG-expressing cancer cells to treatment with anticancer drugs or inhibit tumorigenesis and cancer cell proliferation are provided. Compositions containing these peptides, portions thereof or mimetics thereof are also provided. Methods for use of these peptides or portions thereof, compositions, and mimetics thereof in potentiating efficacy of anticancer drugs, in particular microtubule inhibitors and hormonal cancer therapies, and in treating cancer are also provided.