We must identify treatment strategies to improve patients’ quality of life and prolong their survival, with the ultimate goal of curing them of their disease. Historically, therapies for myeloproliferative neoplasms (MPN) were mainly aimed at helping patients cope with the detrimental effects of their disease, but did not change the inevitable outcome. In the past 15 years, Srdan Verstovsek, M.D., Ph.D. has conducted more than 50 clinical trials testing new therapies, including the JAK1/2 inhibitor, ruxolitinib, which was approved by the FDA for myelofibrosis (MF) in 2011 and for polycythemia vera (PV) in 2014. Verstovsek has also been involved in the clinical development of two other JAK inhibitors (momelotinib and pacritinib) that may be approved in the next few years.
Ruxolitinib and other JAK inhibitors have significantly improved quality of life and prolonged survival for many patients with MF, but it is not a cure. The discovery of several gene mutations in patients with MPNs (JAK2, CALR, MPL, ASXL1, SRSF2, EZH2 and others) provide new targets for drug development, making this an exciting time for MPN research. The logical next step in improving on current treatments for MPN is to combine ruxolitinib with novel drugs that target cellular processes affected by these mutations in order to further improve on the benefits of JAK inhibitors. Studies of new drug combinations are imperative since some patients do not respond to ruxolitinib and many who do respond may eventually lose their response. Verstovsek is paving the way and has already opened clinical trials testing ruxolitinib in combination with other agents.
MPN Laboratory Members
Taghi Manshouri, Laboratory Manager
Ying Zhang, Research Scientist (not pictured)
Sanja Prijic, Postdoctoral Fellow
Ivo Veletic, Postdoctoral Fellow
Joseph Bove, Research Assistant
Verstovsek’s laboratory houses a large number of tissue and blood samples collected from patients with MPN. These samples are also cataloged in a database that includes information on patient demographics, disease stage and characteristics, responses to treatment, time to progression and other valuable clinical information (e.g., blood counts). During the past five years, we have made several exciting discoveries in the laboratory that we believe will shed light on how and why MPNs develop. Understanding at the cellular and molecular level how cancer develops is the key to developing effective and potentially curative therapies. However, this is painstaking work that requires a focused and concerted effort by many people with expertise in basic science research. While finding the answers often takes several years, we believe the time and energy spent is well worth the effort. Without an understanding of the fundamental mechanism by which MPNs develop, we cannot hope to cure the disease.
Understanding the Cause of Bone Marrow Fibrosis
A main focus of our laboratory research is to understand what causes bone marrow fibrosis, which ultimately leads to failure of the bone marrow to produce blood cells.
Recent evidence suggests that spindle-shaped cells called fibrocytes may be responsible for the formation of fibrosis. Our laboratory is testing this idea using a mouse model of myelofibrosis. We are in the process of identifying genes that may be important for the function of these cells and the development of fibrosis. In addition, we can use our mouse model to test drugs that may be effective in myelofibrosis.
In the short term, our studies could provide justification for testing currently available drugs in patients with myelofibrosis. In the long term, our findings could provide information leading to the development of new drugs that may reverse or prevent bone marrow fibrosis in a variety of diseases.