Lucas et al explored the clonal dynamics of chronic lymphocytic leukemia (CLL) patients following treatment and subsequent acquired resistance to ibrutinib and then venetoclax. They report different patterns of resistance mutations from previously reported changes following venetoclax treatment in the absence of prior BTK inhibitor therapy.

EGFR tyrosine kinase inhibitors cause dramatic responses in EGFR-mutant lung cancer, but resistance universally develops. The involvement of β-catenin in EGFR TKI resistance has been previously reported, however, the precise mechanism by which β-catenin activation contributes to EGFR TKI resistance is not clear. Here, we show that EGFR inhibition results in the activation of β-catenin signaling in a Notch3-dependent manner, which facilitates the survival of a subset of cells that we call “adaptive persisters”. We previously reported that EGFR-TKI treatment rapidly activates Notch3, and here we describe the physical association of Notch3 with β-catenin, leading to increased stability and activation of β-catenin. We demonstrate that the combination of EGFR-TKI and a β-catenin inhibitor inhibits the development of these adaptive persisters, decreases tumor burden, improves recurrence free survival, and overall survival in xenograft models. These results supports combined EGFR-TKI and β-catenin inhibition in patients with EGFR mutant lung cancer.

To explore the adaptability of bread wheat to dehydration stress, we screened 28 cultivars collected from different agroclimatic zones, on the basis of malonaldehyde content as biochemical marker in roots of wheat seedlings during germination and classified them as highly tolerant, tolerant, sensitive and highly sensitive. From this primary screening, ten cultivars that showed differential responses to dehydration stress were selected to understand the biochemical and physiological basis of stress tolerance mechanisms. The highly tolerant cultivars showed lower levels of lipid peroxidation, less membrane damage, increased levels of antioxidants, enzymes like catalase, ascorbate peroxidase, glutathione reductase activities, and maintained higher relative water content in comparison to sensitive cultivars, indicating better protection mechanism operating in tolerant cultivars. Correspondingly, highly tolerant cultivars exhibited more accumulation of proline and less H2O2 content across different time points of polyethylene glycol treatments in comparison to sensitive ones. The above biochemical and physiological parameters were further validated through northern analysis of catalase (CAT1) gene, that showed differential expression patterns in tolerant and sensitive cultivars largely in confirmation with the biochemical and physiological analyses. Our study positively correlates the differences in the redox status and antioxidant defense system between tolerant and sensitive cultivars for the establishment of wheat seedlings in typical dehydration conditions.

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