High-throughput screening for drug discovery targeting the cancer cell-microenvironment interactions in hematological cancers.

Introduction The interactions between leukemic blasts and cells within the bone marrow environment affect oncogenesis, cancer stem cell survival, as well as drug resistance in hematological cancers. The importance of this interaction is increasingly being recognized as a potentially important target for future drug discoveries and developments. Recent innovations in the high throughput drug screening-related technologies, novel ex-vivo disease-models, and freely available machine-learning algorithms are advancing the drug discovery process by targeting earlier undruggable proteins, complex pathways, as well as physical interactions (e.g. leukemic cell-bone microenvironment interaction). Area covered In this review, the authors discuss the recent methodological advancements and existing challenges to target specialized hematopoietic niches within the bone marrow during leukemia and suggest how such methods can be used to identify drugs targeting leukemic cell-bone microenvironment interactions. Expert opinion The recent development in cell-cell communication scoring technology and culture conditions can speed up the drug discovery by targeting the cell-microenvironment interaction. However, to accelerate this process, collecting clinical-relevant patient tissues, developing culture model systems, and implementing computational algorithms, especially trained to predict drugs and their combination targeting the cancer cell-bone microenvironment interaction are needed.