Researchers at the University of South Australia’s Centre for Cancer Biology are focusing on structure-based drug discovery approaches to develop more effective treatments for myeloproliferative neoplasms (MPN), a group of blood cancers, according to a study published in Blood Cancer Discovery in 2023.
The research, led by Dr. Denis Tvorogov, a Senior Research Fellow at the Centre for Cancer Biology, examines next-generation JAK2 inhibitors. These inhibitors target the Janus kinase 2 (JAK2) enzyme, which plays a role in the development of MPNs, particularly in cases with the JAK2 V617F mutation. The study evaluates existing type I JAK2 inhibitors – fedratinib and pacritinib – as well as type II inhibitors and pseudokinase inhibitors currently in development.
Current JAK inhibitors, while effective in managing symptoms, do not eradicate the disease, largely due to a lack of strong selectivity for the mutant clone. Dr. Tvorogov’s work leverages recent structural studies that reveal the importance of JAK2 domains beyond the kinase domain in driving the disease process. The research team is utilizing full-length JAK homodimeric structures to design inhibitors with improved selectivity and specificity for mutated JAK2.
The Centre for Cancer Biology’s Cytokine Receptor Laboratory, where Dr. Tvorogov is based, investigates signaling errors responsible for blood cell diseases like acute myeloid leukemia and MPNs, as well as solid cancers such as breast cancer. The lab’s research also extends to chronic inflammatory conditions affecting the lungs and upper respiratory tract.
According to his profile on the Adelaide University website, Dr. Tvorogov’s research has garnered over 1,700 citations. ResearchGate lists 40 research works attributed to him. His h-index, a measure of the impact of his research, is 23, with over 2,000 citations and 38 published papers.
The laboratory collaborates closely with SA Pathology, the Royal Adelaide Hospital, the University of Adelaide, and SAHMRI. These collaborations aim to translate research findings into new diagnostics and treatments, working with pharmaceutical companies like CSL. The lab’s focus is on understanding the fundamental errors in cell signaling that drive cancer and chronic inflammation, with the ultimate goal of improving long-term clinical management and potentially finding cures.
