Novel Drugs Targeting the Microenvironment and the Epigenetic Changes in Hematopoietic Malignancies

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Background

Hematopoietic malignancies are cancers of the hematopoietic and lymphopoietic systems, including leukemias, both acute and chronic, as well as lymphomas, myelomas and plasma cell dyscrasia. These malignancies are difficult to treat, primarily because the underlying molecular mechanisms driving clinical outcome are still poorly understood. Growing evidence suggests that the tissue microenvironment has a role in the biological behavior of the tumor. The main clinical issue is to identify the best target for therapeutic approaches. This fact emphasizes the need for improved diagnostic and prognostic markers, as well as improved understanding of cancer environment, including the cross-talk between malignant cells and stromal cells. In hematological malignancies, the local tumor microenvironment is the key to understanding the disease, explaining its biology from dissemination to resistance to chemotherapy. By the proper understanding and targeting of the tumor microenvironment, the outcome of therapy may be much improved. One example is the success story of acute promyelocytic leukemia, a malignancy treated nowadays with chemotherapy plus differentiation factors. By adding all-trans-retinoic acid (ATRA) to the conventional chemotherapy regimen, the response rate has increased from 60% to more than 90%, being today considered a curable disease, if treated in time. The tumor microenvironment is paramount in the progression and dissemination of hematopoietic malignancies and accumulating evidence indicates that epigenetic phenomena such as microRNAs are extremely important in cancer homeostasis.

Cutting edge research addresses today the field of immunotherapy, but a closer look should be given to the tumor microenvironment, where tumor-initiating cells reside, acquire resistance to therapy and gain the ability to disseminate. By targeting these cells, as well as the surrounding cells, as is the case of tumor-associated fibroblasts, endothelial cells and immune cells, the therapeutic ratio has the potential to be increase. This Research Topic aims to present the tumor microenvironment, as well as the state-of-the-art knowledge in its pharmacological targets, ranging from pre-clinical assays to phase I-III clinical trials.

Through the improved understanding of the molecular mechanisms, as is the case of retinoic acid and PML-RAR alpha in acute promyelocytic leukemia, involved in the microenvironment-mediated promotion of cancer growth and metastasis, novel targets for therapeutic intervention or early diagnosis are presented in this Research Topic, in order to provide scientists state-of-the-art research and the clinical applications on the epigenetics changes of the tumor microenvironment in hematopoietic malignancies. The Research Topic will include Original Research, both pre-clinical and well as phase I-III clinical trials, as well as Reviews and Mini-Reviews, that will present modern approaches to targeting the malignant microenvironment in hematological cancers.

Keywords: Tumor microenvironment, novel drugs, epigenetic changes, hematopoietic progenitors, translational research

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