acalisib (GS-9820) / Gilead - LARVOL DELTA

Elucidating the role of KCTD10 in coronary atherosclerosis: Harnessing bioinformatics and machine learning to advance understanding. (PubMed, Sci Rep) - "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."

Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Immunology • Inflammation • Oncology • CD4

Integrative bioinformatics and machine learning approach unveils potential biomarkers linking coronary atherosclerosis and fatty acid metabolism-associated gene. (PubMed, J Cardiothorac Surg) - "This research has successfully identified seven key FAMGs implicated in AS, offering novel insights into the pathophysiology of the disease. These findings not only contribute to our understanding of AS but also present potential biomarkers for the disease, opening avenues for more effective monitoring and progression tracking of AS."

Biomarker • Journal • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Inflammation • ACSL3 • ALDH2

Inhibition of BCL2 and XPO1 demonstrates synergistic effects in triple-negative breast cancer cell lines (AACR 2024) - "The aim of this study was to evaluate eltanexor (Elta), an XPO1 inhibitor, in combination with venetoclax (Ven), a Bcl-2 inhibitor to promote apoptosis in TNBC models. CellTiter-Glo Cell Viability Assay was utilized to determine cell viability in 6 TNBC cell lines after 72-hour exposure to no drug, Elta, Ven or the combination...Synergy was observed in CAL-120, BT-20, and MDA-MB-468 cell lines, with synergy score values ranging from -13.22 - 25.07... The combination of Elta and Ven resulted in increased apoptosis and antiproliferative activity in TNBC cell lines. Combined, the two drugs synergistically functioned to increase DNA damage and promote apoptotic cell death. This work supports the continued evaluation of Elta and Ven in TNBC."

IO biomarker • Preclinical • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ANXA5 • BCL2 • HER-2 • MCL1 • PGR

Unlocking potential biomarkers bridging coronary atherosclerosis and pyrimidine metabolism-associated genes through an integrated bioinformatics and machine learning approach. (PubMed, BMC Cardiovasc Disord) - "In conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis."

Biomarker • Journal • Machine learning • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Dyslipidemia • Inflammation • Metabolic Disorders • CMPK1 • NT5C2 • RRM1

GEMIN4, a potential therapeutic targets for patients with basal-like subtype breast cancer. (PubMed, BMC Womens Health) - "We hypothesized that GEMIN4 may be the potential target for the treatment of BLBC."

Journal • Breast Cancer • Oncology • Solid Tumor

Role of the SEC62 gene in the migration and proliferation of triple negative and Her2/positive breast cancer cells (GSS 2023) - "In the analyzes of the mean values ​​of the genilcing experiments of the CAL120 cell line, the expected negative effect of the SEC62-Sirna on cell migration is confirmed, while, as expected, the effect on cell proliferation with decreasing SEC62 content remains unchanged. Increased migration and thus also invasion potential seems to be confirmed for triple negative breast cancer."

Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

Effect of 3q oncogene SEC62 on migration and proliferation of triple-negative breast cancer cells (SABCS 2022) - "Material& Methods In this study, three SEC62 gene silencing experiments each with two different siRNAs directed against the SEC62 mRNA were carried out in comparison to a control siRNA in combination with cell proliferation and cell migration tests plus Western blots for the triple- negative breast cancer cell line CAL120 in order to determine the suspected causal relationship between SEC62- overexpression and an increased cell migration and thus an enhanced invasion potential of the cancer cells...Conclusion In this in vitro study using cell migration and cell proliferation assays we found a correlation between SEC62 overexpression and increased cell migration. This implies a potential association between Sec62 and an increased tumor cell invasion in triple-negative breast cancer."

Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

Bcl-xL inhibition radiosensitizes PIK3CA/PTEN wild-type triple negative breast cancers with low Mcl-1 expression. (PubMed, Cancer Res Commun) - "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."

IO biomarker • Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • AKT1 • BCL2 • BCL2L1 • CASP3 • MCL1 • PIK3CA • PTEN

Comprehensive analysis of the ceRNA network in coronary artery disease. (PubMed, Sci Rep) - "In addition, two mRNA datasets which named GSE113079 (98 CAD samples) and GSE9820 (8 CAD samples) were selected to search the differentially expressed genes (DEGs)...GO and KEGG results showed that genes in ceRNA networks were mainly involved in nitrogen compound metabolic process, PI3K-Akt signaling pathway and retrograde endocannabinoid signaling. These findings will improve the understanding of the occurrence and development mechanism of CAD."

Journal • Cardiovascular • Coronary Artery Disease • Heart Failure • H19 • KCNQ1OT1

High miR-30 Expression Associates with Improved Breast Cancer Patient Survival and Treatment Outcome. (PubMed, Cancers (Basel)) - "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."

Clinical • Journal • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • MIR30D • MIR30E

[VIRTUAL] CDK4/6 inhibition radiosensitizes RB1 wild type triple negative breast cancers through impaired homologous recombination (AACR 2021) - "In vivo efficacy of CDK4/6 inhibition + RT was assessed using TNBC patient-derived xenograft models (PDX4664). Although most TNBC cell lines are resistant to CDK4/6 inhibitor monotherapy (IC50 > 250nM) compared to ER+ cells, treatment with 250nM-1μM palbociclib radiosensitized RB1 wild type TNBC (MDA-MB-231, CAL-51, SUM-159, CAL-120; rER 1.08 – 2.22) but failed to radiosensitize RB1 mutant TNBC (CAL-851, MDA-MB-468; rER: 0.84 – 1.00). Radiosensitization of TNBC cell lines also occurred with short term ribociclib or abemaciclib pretreatment... In TNBC, CDK4/6 inhibition and RT leads to suppression of HR activity in an RB1-dependent manner. While ongoing studies seek to elucidate the role of RB1 in HR suppression in the context of CDK4/6 inhibitor-mediated radiosensitization of TNBC, our data suggests that CDK4/6 inhibition + RT could be a valuable clinical strategy to radiosensitize a wide range of breast cancer subtypes, including RB1 wild type TNBC."

Breast Cancer • Estrogen Receptor Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • RAD51 • RB1

Roll Over Study to Provide Idelalisib to Participants Previously Treated With the Investigational PI3Kδ Inhibitor, GS-9820 (clinicaltrials.gov) - P4; N=3; Active, not recruiting; Sponsor: Gilead Sciences; Trial primary completion date: Apr 2017 ➔ Dec 2017

Trial primary completion date • Biosimilar • Oncology

Roll Over Study to Provide Idelalisib to Participants Previously Treated With the Investigational PI3Kδ Inhibitor, GS-9820 (clinicaltrials.gov) - P4; N=3; Terminated; Sponsor: Gilead Sciences; Completed ➔ Terminated

Clinical • Trial termination