Drugs & aging
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Review
Current Status of Bruton's Tyrosine Kinase Inhibitor Development and Use in B-Cell Malignancies.
The B-cell receptor (BCR) pathway plays an important role in the survival, proliferation and trafficking of cancer cells in a variety of B-cell malignancies. Recently, a number of agents have been developed to target various components of the BCR pathway. One such target is Bruton's tyrosine kinase (BTK), a Tec family kinase member found near the cell membrane that is involved in upstream BCR signaling. ⋯ Studies evaluating other potential indications for BTK inhibition are ongoing, including in post-allogeneic hematopoietic stem cell transplant patients for whom ibrutinib may be effective in modulating graft-versus-host disease. Combination trials of ibrutinib with venetoclax, a Bcl-2 inhibitor, are underway and are supported by sound preclinical rationale. Several next-generation BTK inhibitors are under development with the goal of decreasing treatment-related toxicity and resistance.
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Amyotrophic lateral sclerosis (ALS), with its certain prognosis and swift progression, raises concerns regarding the adequacy of pharmacological treatment, including the risk-benefit profiles of prescribed drugs. ⋯ Future research is needed to assess the time to benefit of treatments and to develop guidelines for medication discontinuation in advanced ALS.