Dual Drug Targeting to Kill Colon Cancer Cells
Burgess, A. W.; Faux, M. C.; Corona, S. P.; Weinstock, J.; Lessene, G.; Walker, F.
Show abstract
Colorectal cancer (CRC) is driven by a small set of oncogenic and tumor suppressor mutations. However, different combinations of mutations often lead to poor tumor responses to individual anti-cancer drugs. We have investigated the anti-proliferative and in vitro cytotoxic activity of pair-wise combinations of inhibitors which target specific signalling pathways. Colon cancer cells in non-adherent cultures were killed more effectively by combinations of pyrvinium pamoate (a Wnt pathway inhibitor) and ABT263 (a pro-apoptotic Bcl-2 family inhibitor) or Ly29004 (a PI3kinase inhibitor). However, in a mouse xenograft model, the formulation and toxicity of the ABT737/PP combination prevent the use of these drugs for treatment of tumors. Fortunately, oral analogues of PP (pyrvinium phosphate, PPh) and ABT737(ABT263) have equivalent activity and can be used for treatment of mice carrying SW620 colorectal cancer xenografts. The PPh/ABT263 induced SW620 tumor cell apoptosis and reduced the rate of SW620 tumor growth. Combinations of Wnt signaling inhibitors and specific inhibitor of pro-survival proteins should be considered for the treatment of precancerous colon adenomas and advanced colorectal cancers with APC mutations.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Selective Impact of ALK and MELK Inhibition on ERα Stability and Cell Proliferation in Cell Lines Representing Distinct Molecular Phenotypes of Breast Cancer 94%
- Periostin facilitates ovarian cancer recurrence by enhancing cancer stemness 94%
- Epithelial-mesenchymal transition sensitizes breast cancer cells to cell death via the fungus-derived sesterterpenoid ophiobolin A 94%
Similar papers in this journal
- Differences in durability of PARP inhibition by clinically approved PARP inhibitors: implications for combinations and scheduling 94%
- Suppression of Ovarian Cancer Cell Proliferation is Associated with Upregulation of Cell-Matrix Adhesion Programs and Integrin-β4-Induced Cell Protection from Cisplatin. 94%
- A model of Zebrafish Avatar for co-clinical trials 94%
Similar papers in this journal
- A Priori Activation of Apoptosis Pathways of Tumor (AAAPT) Technology: Development of Targeted Apoptosis Initiators for Cancer Treatment. 96%
- A phosphoramidate modification of FUDR, NUC-3373, causes DNA damage and DAMPs release from colorectal cancer cells, potentiating lymphocyte-induced cell death 95%
- Altering mammalian transcription networking with ADAADi: An inhibitor of ATP-dependent chromatin remodeling 94%
Similar papers in this journal
- Anticancer efficacy of KRASG12C inhibitors is potentiated by PAK4 inhibitor KPT9274 in preclinical models of KRASG12C mutant pancreatic and lung cancers 95%
- Targeting dormant ovarian cancer cells in vitro and in an in vivo model of platinum resistance 94%
- Immunotherapy with immunocytokines and PD-1 blockade enhances the anticancer activity of small molecule-drug conjugates targeting carbonic anhydrase IX 93%
Similar papers in this journal
- Novel kinome profiling technology reveals drug treatment is patient and 2D/3D model dependent in GBM 94%
- A pro-oxidant combination of resveratrol and copper down-regulates hallmarks of cancer and immune checkpoints in patients with advanced oral cancer: Results of an exploratory study (RESCU 004) 93%
- Augmentation of extracellular ATP synergizes with chemotherapy in triple negative breast cancer 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.