acalisib (GS-9820)

This study successfully discovered nine GlnMgs that are associated with AS. These findings provide valuable insights into potential novel biomarkers for AS and offer prospects for monitoring disease progression.

Using two independent datasets (GSE249956 and GSE98206), differentially expressed genes (DEGs) were identified between ibrutinib-resistant and sensitive CLL samples. In the broader context, PD-1 expression in CLL cells is linked to active proliferation and immune escape. Overall, our findings emphasize PDCD1's central role in ibrutinib resistance through immune checkpoint pathways and support the rationale for combining BTK inhibitors with immune checkpoint blockade therapies in resistant CLL cases.

This research elucidates the complex relationship between KLRD1 and AS, underscoring its potential as a novel biomarker for diagnosing and monitoring the disease.

In our study, KCTD10 was identified as a focal point through an integrative analysis of differentially expressed genes (DEGs) across multiple datasets (GSE43292 and GSE9820) from the GEO database, aligned with immune-related gene sets from the ImmPort database...This research elucidates the complex relationship between KCTD10 and AS, underscoring its potential as a novel biomarker for diagnosing and monitoring the disease. Our findings provide a solid foundation for further investigations, suggesting that targeting KCTD10-related pathways could markedly advance our understanding and management of AS, offering new avenues for therapeutic intervention.

We hypothesized that GEMIN4 may be the potential target for the treatment of BLBC.

We demonstrate that pan Bcl-2 family inhibition (ABT-263, rER: 1.52-1.56) or Bcl-xL specific inhibition (WEHI-539, A-1331852; rER: 1.31-2.00) radiosensitized wild-type PIK3CA/PTEN TNBC (MDA-MB-231, CAL-120) but failed to radiosensitize mutant PIK3CA/PTEN TNBC (rER: 0.90 - 1.07; MDA-MB-468, CAL-51, SUM-159). In vivo, ABT-263 or A-1331852 in combination with RT decreased tumor growth and increased tumor tripling time (p < 0.0001) in PIK3CA/PTEN wild-type TNBC cell line and patient-derived xenografts. Collectively, this study provides the preclinical rationale for early phase clinical trials testing the safety, tolerability, and efficacy of Bcl-xL inhibition and RT in women with wild-type PIK3CA/PTEN wild-type TNBC at high risk for recurrence.

We conducted a two-stage drug-screen to investigate the impact of miR-30 family members (miR-30a-30e) on sensitivity to doxorubicin and lapatinib in six breast cancer cell lines HCC1937, HCC1954, MDA-MB-361, MCF7, MDA-MB-436 and CAL-120, using drug sensitivity scores (DSS) to compare the miR-30 family mimics to their specific inhibitors. According to the pathway analysis, the miR-30 family has a suppressive effect on cell motility and metastasis in breast cancer. Our results suggest prognostic and predictive potential for the miR-30 family, which warrants further investigation.