KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)

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)

17d

Modulating metabolic signatures to mitigate cabozantinib resistance in FLT3-ITD acute myeloid leukemia cell models. (PubMed, Cell Death Discov)

In addition to resistance to cabozantinib, they also exhibited resistance to FDA-approved sorafenib and quizartinib with substantial increases in IC50...Moreover, both omipalisib and radicicol exhibited synergistic effects with cabozantinib, highlighting their therapeutic potential. Overall, we identified metabolic dysregulation as a hallmark of cabozantinib resistance and suggested that targeting metabolic vulnerabilities with PI3K/mTOR or HSP90 inhibitors could be an option to mitigate drug resistance.

17 days ago

Journal

FLT3 (Fms-related tyrosine kinase 3) • GAPDH (Glyceraldehyde-3-Phosphate Dehydrogenase)

sorafenib • Cabometyx (cabozantinib tablet) • Vanflyta (quizartinib) • omipalisib (GSK2126458)

2ms

NCI-2013-02103: Testing the Addition of Navitoclax to the Combination of Dabrafenib and Trametinib in People Who Have BRAF Mutant Melanoma (clinicaltrials.gov)

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2027 | Trial primary completion date: Dec 2025 --> Dec 2027

2 months ago

Trial completion date • Trial primary completion date • IO biomarker

BCL2 (B-cell CLL/lymphoma 2)

BRAF V600E • BRAF V600 • BRAF V600K

THXID® BRAF Kit • cobas® 4800 BRAF V600 Mutation Test

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

3ms

A proteogenomic gene signature defines prognostic subgroups highlighting PI3K/AKT/mTOR signaling pathway as a therapeutic vulnerability in myeloid malignancies. (PubMed, Cell Commun Signal)

Together, our findings revealed shared molecular features across MPN and AML, identified a prognostic gene signature for risk stratification, and provided rationale for PI3K/mTOR inhibition as a promising therapeutic strategy in myeloid malignancies.

3 months ago

Journal • Gene Signature

CDCP1 (CUB Domain Containing Protein 1)

omipalisib (GSK2126458)

3ms

Patient-Derived Xenograft Mouse Model of a Rare Gynecologic Malignancy: Personalized Medicine for the Treatment of Mesonephric-Like Adenocarcinoma. (PubMed, Cureus)

We established a PDX model of MLA to facilitate personalized treatment for rare tumors.

3 months ago

Preclinical • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)

Mekinist (trametinib) • carboplatin • paclitaxel • omipalisib (GSK2126458)

4ms

ADVL1521: Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia (clinicaltrials.gov)

P2, N=10, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Oct 2025 --> Oct 2026

4 months ago

Trial completion date

NF1 (Neurofibromin 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)

RAS mutation • CBL mutation

Mekinist (trametinib) • omipalisib (GSK2126458)

4ms

Targeting serine metabolism vulnerability in omipalisib-resistant acute myeloid leukemia with phosphoglycerate dehydrogenase inhibitors. (PubMed, Biomed Pharmacother)

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.

4 months ago

Journal • IO biomarker

XPO1 (Exportin 1) • PHGDH (Phosphoglycerate Dehydrogenase)

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

5ms

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

5 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)

6ms

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.

6 months ago

Journal

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

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

10ms

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.

10 months ago

Journal

BCL2 (B-cell CLL/lymphoma 2)

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

11ms

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.

11 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

11ms

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

11 months ago

Trial completion date

KRAS (KRAS proto-oncogene GTPase)

KRAS mutation • KRAS G12C • KRAS G12

Mekinist (trametinib) • docetaxel • omipalisib (GSK2126458)