FoxO1 signaling in B cell malignancies and its therapeutic targeting
FoxO1 has context‐specific tumor suppressor or oncogenic character in myeloid and B cell malignancies. This includes tumor‐promoting properties such as stemness maintenance and DNA damage tolerance in acute leukemias, or regulation of cell proliferation and survival, or migration in mature B cell malignancies.
Krystof Hlavac+3 more
wiley +1 more source
Predicting probability distributions for cancer therapy drug selection optimization [PDF]
Large variability between cell lines brings a difficult optimization problem of drug selection for cancer therapy. Standard approaches use prediction of value for this purpose, corresponding e.g. to expected value of their distribution. This article shows superiority of working on, predicting the entire probability distributions - proposing basic tools
arxiv
Insights into PI3K/AKT signaling in B cell development and chronic lymphocytic leukemia
This Review explores how the phosphoinositide 3‐kinase and protein kinase B pathway shapes B cell development and drives chronic lymphocytic leukemia, a common blood cancer. It examines how signaling levels affect disease progression, addresses treatment challenges, and introduces novel experimental strategies to improve therapies and patient outcomes.
Maike Buchner
wiley +1 more source
In Silico Implementation of Evolutionary Paradigm in Therapy Design: Towards Anti-Cancer Therapy as Darwinian Process [PDF]
In here presented in silico study we suggest a way how to implement the evolutionary principles into anti-cancer therapy design. We hypothesize that instead of its ongoing supervised adaptation, the therapy may be constructed as a self-sustaining evolutionary process in a dynamic fitness landscape established implicitly by evolving cancer cells ...
arxiv +1 more source
Diphthamide synthesis is linked to the eEF2‐client chaperone machinery
The diphthamide modification of eukaryotic translation elongation factor 2 (eEF2) is important for accurate protein synthesis. We addressed the potential coordination of de novo eEF2 synthesis with simultaneous or subsequent diphthamide modification. Our work reveals that the co‐chaperones Hgh1 and Cpr7, which are known to support folding of nascent ...
Lars Kaduhr+4 more
wiley +1 more source
Spatial heterogeneity in drug concentrations can facilitate the emergence of resistance to cancer therapy [PDF]
Acquired resistance is one of the major barriers to successful cancer therapy. The development of resistance is commonly attributed to genetic heterogeneity. However, heterogeneity of drug penetration of the tumor microenvironment both on the microscopic level within solid tumors as well as on the macroscopic level across metastases may also contribute
arxiv +1 more source
Characteristics of the Kelch domain containing (KLHDC) subfamily and relationships with diseases
The Kelch protein superfamily includes 63 members, with the KLHDC subfamily having 10 proteins. While their functions are not fully understood, recent advances in KLHDC2's structure and role in protein degradation have highlighted its potential for drug development, especially in PROTAC therapies.
Courtney Pilcher+6 more
wiley +1 more source
Principled Drug-Drug Interaction Terms for Bayesian Logistic Regression Models of Drug Safety in Oncology Phase I Combination Trials [PDF]
In Oncology, trials evaluating drug combinations are becoming more common. While combination therapies bring the potential for greater efficacy, they also create unique challenges for ensuring drug safety. In Phase-I dose escalation trials of drug combinations, model-based approaches enable efficient use of information gathered, but the models need to ...
arxiv
Taurine promotes glucagon‐like peptide‐1 secretion in enteroendocrine L cells
Taurine, a sulfur‐containing amino acid, is likely taken up by enteroendocrine L cells via the taurine transporter. This process increases the levels of cytosolic ATP. The increase in intracellular Ca2+ concentrations and glucagon‐like peptide‐1 secretion through membrane depolarization is caused by the closure of ATP‐sensitive potassium channels ...
Yuri Osuga+6 more
wiley +1 more source
Prospect for application of mathematical models in combination cancer treatments [PDF]
The long-term efficacy of targeted therapeutics for cancer treatment can be significantly limited by the type of therapy and development of drug resistance, inter alia. Experimental studies indicate that the factors enhancing acquisition of drug resistance in cancer cells include cell heterogeneity, drug target alteration, drug inactivation, DNA damage
arxiv