Combinatorial nanocarriers against drug resistance in hematological cancers: Opportunities and emerging strategies

Hematological cancers are a group of malignancies affecting human hematopoietic and lymphoid tissues. Although the patients respond to treatment regimen during initial phases, the hematoma tumor heterogeneity results in the presence of some minimal disease residue thereby exhibiting remission, relapses or refractoriness in disease conditions leading to poor overall survival period. The current therapeutic standard practices involve blending of conventional agents with novel targeting agents or immune-therapeutics in a cocktail to effectively reap the benefits of drugs acting through multiple signaling pathways. Considerable evaluation of the risk benefit ratio on part of clinicians is necessitated to select the best optimum therapy considering the high incidences of drug resistance. This drug resistance may be attributed to faulty upregulation or mutation of multiple drug resistance regulating genes, increased tumor cell immune system cross talk, increased expression of drug efflux pump inducers and inhibition of apoptosis among others. Conventional single drug nanotherapeutics as modulators of drug resistance have already clinically exhibited their potential by passively delivering the active cargo to desired targets in hematological neoplasms. However, with the ever-growing clinical failures of such therapies, the landscape of hematological cancer treatment has seen a plethora of changes in the last few years. The two towering changes in the treatment has been the approval of combinatorial drug nanocarrier Vyxeos™ and chimeric antigen receptor T cell (CAR-T) therapy Kymriah™ as well as Yescarta™. The approval of CAR-T therapy not only resulted in a paradigm shift in the avenues of blood cancer treatment towards personalized approaches but also saddled it with questions of economic viability and effectiveness in the entire spectrum of such neoplasms. Under such conditions, combinatorial drug nanocarriers encompassing synergistic ratios of clinically effective drug combinations affording temporal and spatial control present an exciting approach to overcome these drug resistance modalities. This platform provides increased chances of therapeutic in-vitro in-vivo correlation along with minimization of drug resistance and associated disease relapse conditions. The present review intends to present the current preclinical and clinical advances in combinatorial nanocarrier mediated management of drug resistance in hematological cancers.