Disclosed are methods for treating one or more mammalian cancers, and in particular, methods for treating human melanoma, or a head or neck cancer, that employ therapeutically-effective amounts of one or more iNOS pathway-inhibitory compounds, either alone, or in combination with one or more selected antihypertensive agents (including, for example, calcium channel antagonists), alone, or further in combination with one or more conventional chemotherapeutic agents. Also disclosed are pharmaceutical formulations that comprise these compositions, as well as methods for their use in treating refractory, metastatic, and/or relapsed cancers, or, for use in the management or reversal of treatment resistance in one or more such mammalian cancers.