Boolean network modeling in systems pharmacology
AbstractQuantitative systems pharmacology (QSP) is an emerging discipline that aims to discover how drugs modulate the dynamics of biological components in molecular and cellular networks and the impact of those perturbations on human pathophysiology. The integration of systems-based experimental and computational approaches is required to facilitate the advancement of this field. QSP models typically consist of a series of ordinary differential equations (ODE). However, this mathematical framework requires extensive knowledge of parameters pertaining to biological processes, which is often unavailable. An alternative framework that does not require knowledge of system-specific parameters, such as Boolean network modeling, could serve as an initial foundation prior to the development of an ODE-based model. Boolean network models have been shown to efficiently describe, in a qualitative manner, the complex behavior of signal transduction and gene/protein regulatory processes. In addition to providing a starting point prior to quantitative modeling, Boolean network models can also be utilized to discover novel therapeutic targets and combinatorial treatment strategies. Identifying drug targets using a network-based approach could supplement current drug discovery methodologies and help to fill the innovation gap across the pharmaceutical industry. In this review, we discuss the process of developing Boolean network models and the various analyses that can be performed to identi...
Condition: Multiple Myeloma Intervention: Biological: GC012F injection Sponsors: Shanghai Changzheng Hospital; Gracell Biotechnology Ltd. Recruiting
ConclusionTh17 cells contribute to the stratification of different treatment stages of MM patients. The level of Th17 cells in patients with newly diagnosed MM is associated with the treatment outcome of complete remission.
This article summarizes our up-to-date knowledge on the pathophysiologic role of XPO-1 in MM. Furthermore, it reviews the most recent clinical data on selinexor in combination with dexamethasone and other anti-MM agents; and discusses its safety profile, management strategies; and potential future developments.Expert opinion: Selinexor represents a next-generation-novel agent with an innovative mechanism of action that marks a significant advance in the treatment of heavily pretreated MM patients. Ongoing studies investigate its therapeutic potential also in earlier lines of therapy. Additional data is needed to confirm th...
to Use of proteasome inhibitors (PIs) has been the therapeutic backbone of myeloma treatment over the past decade. Many PIs are being developed and evaluated in the preclinical and clinical setting. The first-in-class PI, bortezomib, was approved by the US food and drug administration in 2003. Carfilzomib is a next-generation PI, which selectively and irreversibly inhibits proteasome enzymatic activities in a dose-dependent manner. Ixazomib was the first oral PI to be developed and has a robust efficacy and favorable safety profile in patients with multiple myeloma. These PIs, together with other agents, including alky...
Conclusions: We identified low sXBP1 levels and TP53 abnormalities as factors correlating with bortezomib resistance in MM. Therefore, determination of sXBP1 levels and TP53 status prior to BTZ treatment in MM may be beneficial to predict BTZ resistance.
The agency granted the immunoconjugate targeting B-cell maturation antigen priority review to belantamab mafodotin for the treatment of heavily pre-treated patients with relapsed or refractory multiple myeloma.
This study is the first to divide patients into three patterns, namely, A, B, and C, according to the M- protein reduction rate during the first two therapy cycles. The results showed that pattern B patients with progressive reduction in M-protein had better progression-free survival (PFS) and overall survival (OS) than did pattern A or C patients with precipitating or slow M-protein reduction (75.33 ± 18.81 versus 41.23 ± 9.13 or 26.60 ± 6.67 months;P
Cancer Gene Therapy, Published online: 21 January 2020; doi:10.1038/s41417-020-0162-2Prognostic role of minichromosome maintenance family in multiple myeloma
In this study, we demonstrate that both the APC and the antigen loading method (peptide pulsing versus full-length mRNA transfection) to analyze T-cell functional avidity have a significant impact on the EC50 values of a given TCR. For rapid assessment of the functional avidity of a cloned TCR towards its endogenously processed MHC I-restricted epitope, we showcase that the TAA mRNA-transfected U266 cell line is a suitable and versatile model APC.