Furthermore, we found that, like OCI-AML cells, the exportin 1 (XPO1) inhibitors selinexor and eltanexor significantly induced cell cycle arrest and reduced PHGDH expression in OCI-AML3-OR cells. Therefore, treatment with PHGDH inhibitors could be a therapeutic strategy for refractory AML to PI3K/mTOR inhibitors. Relevant clinical trials are warranted.

1 month ago

Journal • IO biomarker

XPO1 (Exportin 1) • PHGDH (Phosphoglycerate Dehydrogenase)

Xpovio (selinexor) • omipalisib (GSK2126458) • eltanexor (KPT-8602)

2ms

NCI-MATCH: Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) (clinicaltrials.gov)

P2, N=6452, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026

2 months ago

Trial completion date • Trial primary completion date

MSI (Microsatellite instability) • CD4 (CD4 Molecule)

Opdivo (nivolumab) • Herceptin (trastuzumab) • Mekinist (trametinib) • Xalkori (crizotinib) • Tagrisso (osimertinib) • Gilotrif (afatinib) • Ibrance (palbociclib) • dasatinib • Tafinlar (dabrafenib) • Vitrakvi (larotrectinib) • sunitinib • Kadcyla (ado-trastuzumab emtansine) • Balversa (erdafitinib) • Mektovi (binimetinib) • adavosertib (AZD1775) • Truqap (capivasertib) • Aliqopa (copanlisib) • fexagratinib (ABSK091) • sapanisertib (CB-228) • ipatasertib (RG7440) • taselisib (GDC-0032) • omipalisib (GSK2126458) • ulixertinib (BVD-523) • Erivedge (vismodegib) • Trazimera (trastuzumab-qyyp) • Fakzynja (defactinib) • GSK2636771 • Paletan (pertuzumab biosimilar) • relatlimab (BMS-986016) • ABP 206 (nivolumab biosimilar) • Pertuvia (pertuzumab biosimilar)

3ms

Changes in Melanoma Cell Morphology Following Inhibition of Cell Invasion by Third-Generation mTOR Kinase Inhibitors. (PubMed, Int J Mol Sci)

The study used mTOR kinase inhibitors: Everolimus and Torkinib; dual PI3K/mTOR inhibitors BEZ-235 and Omipalisib; and the mTORC1/2 inhibitor OSI-027. These compounds were used both as monotherapy and in combination with the MEK1/2 inhibitor AS-703026...The morphology of cells also changed significantly: their thickness, volume, roughness, convexity of shape, and irregularity, which may be a good diagnostic and prognostic factor for the response to treatment. Our studies to date on the effect of three generations of mTOR kinase inhibitors on the inhibition of the invasion process, the activation of apoptosis, and the reduction in cell proliferation suggest that they may be an important target for anticancer therapy.

3 months ago

Journal

MMP2 (Matrix metallopeptidase 2) • MMP9 (Matrix metallopeptidase 9)

everolimus • dactolisib (RTB101) • omipalisib (GSK2126458) • pimasertib (AS703026) • AVTX-006 • torkinib (PP242)

7ms

Navitoclax, a Bcl-2/xL Inhibitor, and YM155, a Survivin Inhibitor, in Combination with Carboplatin, Effectively Inhibit Ovarian Cancer Tumor Growth. (PubMed, Mol Cancer Ther)

Initial results showed that omipalisib, verteporfin, CA3, mitoxantrone, navitoclax, venetoclax, and YM155 had significant single-drug activity in either the ALDHlo or both the ALDHlo/ALDHhi cell populations...In vivo, the combination of navitoclax/YM155/carboplatin decreased ovarian cancer metastasis, decreased the percentage of ALDHhi ovarian cancer cells in tumors, and increased survival when compared with carboplatin treatment alone in xenograft models. Our results suggest that the combination of navitoclax/YM155/carboplatin has promise as a therapy for treating ovarian cancer.

7 months ago

Journal

BCL2 (B-cell CLL/lymphoma 2)

Venclexta (venetoclax) • carboplatin • navitoclax (ABT 263) • omipalisib (GSK2126458) • mitoxantrone • Visudyne (verteporfin) • sepantronium bromide (PC-002)

8ms

Combined Omipalisib and MAPK Inhibition Suppress PDAC Growth. (PubMed, Cancers (Basel))

In vivo oral administration of combined Omipalisib/Trametinib treatment was significantly more effective than Omipalisib/SHP099 in reducing implanted tumor growth, and the Omipalisib/Trametinib treatment more effectively reduced tumor progression and prolonged survival in an aggressive genetically engineered mouse model of PDAC than either Omipalisib or Trametinib alone. Altogether, our data support a rationale for a dual treatment strategy targeting both PI3K and MAPK pathways in pancreatic cancers.

8 months ago

Journal

KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

KRAS mutation

Mekinist (trametinib) • omipalisib (GSK2126458) • SHP099

8ms

Trametinib and Docetaxel in Treating Patients With Recurrent or Stage IV KRAS Mutation Positive Non-small Cell Lung Cancer (clinicaltrials.gov)

P2, N=60, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

8 months ago

Trial completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Mekinist (trametinib) • docetaxel • omipalisib (GSK2126458)

9ms

Trametinib and Navitoclax in Treating Patients With Advanced or Metastatic Solid Tumors (clinicaltrials.gov)

P1/2, N=96, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2025 --> Mar 2026

9 months ago

Trial completion date • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BCL2L2 (BCL2 Like 2)

KRAS mutation • NRAS mutation

Mekinist (trametinib) • navitoclax (ABT 263) • omipalisib (GSK2126458)

9ms

InfoScan: A New Transcript Identification Tool Based on scRNA-Seq and Its Application in Glioblastoma. (PubMed, Int J Mol Sci)

Drug sensitivity assays indicated that neoplastic-stemness cells might be sensitive to omipalisib, a PI3K inhibitor, pointing to a potential therapeutic target. InfoScan offers a robust framework for exploring complex transcriptomic landscapes and characterizing rare cell populations, providing valuable insights into GBM biology and advancing precision cancer therapy.

9 months ago

Journal

SPP1 (Secreted Phosphoprotein 1)

omipalisib (GSK2126458)

9ms

Trametinib in Increasing Tumoral Iodine Incorporation in Patients With Recurrent or Metastatic Thyroid Cancer (clinicaltrials.gov)

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2025 --> Jan 2026

9 months ago

Trial completion date

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • EGF (Epidermal growth factor)

KRAS mutation • NRAS mutation • BRAF V600 • BRAF wild-type • RAS wild-type • HRAS mutation • KRAS G12 • NRAS Q61 • KRAS G13 • NRAS G12 • NRAS G13 • KRAS Q61

Mekinist (trametinib) • omipalisib (GSK2126458)

10ms

Trametinib in Treating Patients With Advanced Cancer With or Without Hepatic Dysfunction (clinicaltrials.gov)

P1, N=46, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Dec 2025 --> Dec 2024

10 months ago

Trial completion • Trial completion date

BRAF (B-raf proto-oncogene)

BRAF V600E • BRAF V600

Mekinist (trametinib) • omipalisib (GSK2126458)