- |||||||||| Journal: Effects of evodiamine on PI3K/Akt and MAPK/ERK signaling pathways in pancreatic cancer cells. (Pubmed Central) - Oct 7, 2020
The tumor expression of phosphorylated AKT, detected using immunohistochemistry, decreased with increasing EVO doses in vivo. EVO induced PC cell apoptosis by inhibiting phosphoinositide 3‑kinase/AKT and mitogen‑activated protein kinase/ERK and inhibiting the phosphorylation of signal transducer and activator of transcription activator 3 in PC cells to inhibit autophagy, suggesting that EVO may be considered as a novel PC treatment.
- |||||||||| Journal: WAVE3 phosphorylation regulates the interplay between PI3K, TGF-β, and EGF signaling pathways in breast cancer. (Pubmed Central) - Oct 7, 2020
More importantly, we found that WAVE3 phosphorylation is also required for the activation of PI3K, TGF-β, and EGF signaling and their respective downstream effectors. Therefore, our study identified a novel function for WAVE3 in the regulation of breast cancer development and progression through the modulation of a positive feedback loop between WAVE3 and PI3K-TGF-β-EGF signaling pathways.
- |||||||||| Piqray (alpelisib) / Novartis
Trial completion date, Combination therapy, Metastases: BYL719 and Letrozole in Post-Menopausal Patients With Hormone Receptor-Positive Metastatic Breast Cancer (clinicaltrials.gov) - Oct 7, 2020 P1, N=46, Active, not recruiting, Given the fact that PBI-05204 has already been examined in phase I and II clinical trials for cancer patients, its efficacy when combined with standard of care chemotherapy and radiotherapy should be explored in future clinical trials of this difficult to treat brain cancer. Trial completion date: Sep 2020 --> Sep 2021
- |||||||||| Biomarker, Journal: COL6A6 interacted with P4HA3 to suppress the growth and metastasis of pituitary adenoma via blocking PI3K-Akt pathway. (Pubmed Central) - Oct 4, 2020
In addition, P4HA3 worked as the upstream of the PI3K-Akt pathway to alleviate the antitumor activity of COL6A6 on the growth and metastasis of both AtT-20 and HP75 cells. Furthermore, the inhibitory effect of COL6A6 on cell proliferation, migration and invasion, and epithelial-mesenchymal transition (EMT) was reversed by P4HA3 overexpression or activation of the PI3K-Akt pathway induced by IGF-1 addition, which provided a new biomarker for clinical PA treatment.
- |||||||||| Koselugo (selumetinib) / Merck (MSD), AstraZeneca, docetaxel / Generic mfg.
Clinical, Journal: Defining subpopulations of differential drug response to reveal novel target populations. (Pubmed Central) - Oct 4, 2020 A systematic analysis of preclinical data for a failed phase III trial of selumetinib combined with docetaxel in lung cancer suggests potential indications in pancreatic and colorectal cancers with KRAS mutation. This data-informed study exemplifies a method for stratified medicine to identify novel cancer subpopulations, their genetic biomarkers, and effective drug combinations.
- |||||||||| Piqray (alpelisib) / Novartis
Journal: Frequency and spectrum of PIK3CA somatic mutations in breast cancer. (Pubmed Central) - Oct 3, 2020 PIK3CA mutations in BC are heterogenous and ~ 20% of patients with a known PIK3CA mutation, and 95% with a known double PIK3CAmut tumor, would not be captured by the therascreen panel. Finally, the clinical utility of PIK3CA mutations not present in the therascreen companion diagnostic assay or identified by other sequencing-based assays needs further investigation.
- |||||||||| Herceptin (trastuzumab) / Roche, Perjeta (pertuzumab) / Roche, Aliqopa (copanlisib) / Bayer
[VIRTUAL] Phase Ib/II trial of copanlisib in combination with trastuzumab and pertuzumab after induction treatment of HER2 positive metastatic breast cancer with PIK3CA mutation or PTEN mutation () - Oct 2, 2020 - Abstract #SABCS2020SABCS_1150; In the phase III CLEOPATRA trial, while the combination of pertuzumab (P) plus trastuzumab (H) plus docetaxel (T) as compared with trastuzumab (H) plus docetaxel (T), significantly prolonged PFS (18.5 vs 12.4 months) for first-line treatment for HER2-positive (+ve) metastatic breast cancer (MBC), longer median PFS was observed in patients with wildtype versus mutated PIK3CA in both the control (13.8 v 8.6 months) and pertuzumab groups (21.8 v 12.5 months)...To have 82 evaluable patients with a 15% dropout rate, we would need to enroll 96 patients. A Wieand rule futility interim analysis will be conducted when half of the total of 54 required PFS events are observed.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
[VIRTUAL] Trastuzumab deruxtecan (T-DXd; DS-8201) in combination with other anticancer agents in patients with HER2-low metastatic breast cancer: A phase 1b, open-label, multicenter, dose-finding and dose-expansion study (DESTINY-Breast08) () - Oct 2, 2020 - Abstract #SABCS2020SABCS_1083; Module 3 (HR−): only 1 prior line of CTX for mBC Modules 4 and 5 (HR+): only 1 prior line of ET but no prior CTX for mBC The primary endpoint in part 1 is safety and tolerability and determination of RP2Ds. In part 2, the primary endpoint is safety and tolerability, and secondary endpoints include ORR, duration of response, and PFS (all by investigator assessment according to RECIST 1.1) as well as overall survival, PK, and immunogenicity.
- |||||||||| MEN1611 / Menarini, Herceptin (trastuzumab) / Roche
[VIRTUAL] Men1611 promotes immune activating myeloid cell polarization (OnDemand) - Oct 2, 2020 - Abstract #SABCS2020SABCS_1024; In preclinical models, MEN1611 has demonstrated a long lasting antitumor activity when combined with trastuzumab in HER2+/PiK3CA mutated breast cancer...Previous evidences have shown that selective targeting of PI3Kγ by IPI-549 can reshape the inflammatory cells infiltrating tumors towards a less immunosuppressive phenotype and promote cytotoxic T cell-mediated tumor regression...In conclusion, we demonstrated in a cellular context that MEN1611 activity on PI3Kγ isoform is responsible for macrophages reprogramming from an immune-suppressive to an immune-activating phenotype. Moreover, we observed that in 4T1 murine breast cancer model, tumor regression induced by MEN1611 was also sustained by a modulation of the inflammatory microenvironment, characterized by an increased recruitment and cytotoxicity of T cells.
- |||||||||| fulvestrant / Generic mfg.
[VIRTUAL] Combination PI3K and NOS targeted therapy for metaplastic breast cancer (OnDemand) - Oct 2, 2020 - Abstract #SABCS2020SABCS_757; Further studies are currently ongoing to elucidate the molecular mechanisms involved in enhanced cell death and decreased tumorigenesis with L-NMMA and alpelisib dual therapy. Our results support the concept that LNMMA and alpelisib combination therapy has therapeutic potential in the treatment of MpBC, which may enable rapid translational into clinical trials, and impact the exceeding poor prognosis of women with MpBC.
- |||||||||| tamoxifen / Generic mfg.
[VIRTUAL] Protein interactome dysregulation analysis reveals putative therapeutic targets for BCI(H/I)-low breast cancers patients (OnDemand) - Oct 2, 2020 - Abstract #SABCS2020SABCS_396; GSEA of the 21 BCI(H/I)-high proteome samples revealed a positive association with the Bowie tamoxifen response, and the α- and γ-interferon response C2 gene sets, while the 23 BCI-H/I-Low samples revealed a positive association (p=0.03, FDRq=0.052) with the hedgehog signaling and the early estrogen Hallmark gene sets... Quantitative mass spectrometry-based protein-protein interaction dysregulation identified the PI3K- pathway as a putative exploitable therapeutic vulnerability in BCI(H/I)-low HR+ BC patients at risk for late disease recurrence.
- |||||||||| vistusertib (AZD2014) / AstraZeneca, Mekinist (trametinib) / Novartis, trametinib
Journal: Combined mTOR/MEK inhibition prevents proliferation and induces apoptosis in NF2-mutant tumors. (Pubmed Central) - Oct 2, 2020 Nevertheless, canonical p-Smad2 was largely repressed in OSCC tumor tissues, suggesting that the activin A-mediated noncanonical pathway is essential for the carcinogenesis of OSCC. We found that PI3K/mTOR inhibitor could decrease the proliferation of NF-2 mutation tumor cell lines by enhancing apoptosis, while the combination of two drugs might have a better effect.
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