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Nově zkoumané možnosti terapie

Peptide-mediated targeting of tumors - Retro-inverso peptides

• Resist protease degradation and maintain their bioactivity

Retro-inverso peptide D(PRPSPKMGVSVS) (D-SP5)

• Targeting ligand to develop gene therapy for gastric adenocarcinoma [9]
• Higher affinity for human gastric adenocarcinoma (SGC7901) cells compared with that of its parental peptide, L(SVSVGMKPSPRP) (L-SP5) [9]
• Polyethylenimine (PEI)/pDNA, polyethylene glycol (mPEG)-PEI/pDNA and D-SP5-PEG-PEI/pDNA were prepared for further study [9]
• Transfection efficiency of D-SP5-PEG-PEI/pGL(4.2) was larger compared with that of mPEG-PEI/pGL(4.2) [9]
• In vivo pharmacodynamics study revealed that D-SP5-PEG-PEI/pTRAIL could inhibit the growth of gastric adenocarcinoma SGC7901 xenografts in nude mice [9]

Onkolytické viry

• Can kill malignant cells while sparing normal cells
• Multiple pathways are involved
• Antitumor effects of viral infection on SGC-7901 and AGS cells were investigated
• Endoplasmic reticulum stress
• Autophagy [10]

Recombinant avirulent Newcastle disease virus (NDV)

• NDV causes a highly infectious disease in poultry worldwide
• In humans it is reported to have oncolytic and immuno-stimulatory effects
• NDV wild-type strain
• LaSota strain
• Expressing the rabies virus glycoprotein (rL-RVG) [10]
• RL-RVG virus group is much more powerful compared with the NDV-infected group
• Therapeutic efficacy in preclinical studies and are currently in clinical trials [12]
• Interleukin-2 (IL-2) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) delivered by rNDV [12]
• Both induced increases in apoptosis, endoplasmic reticulum stress, and autophagy in the SGC-7901 and AGS cells
• RL-RVG and NDV are potent antitumor agents that induce autophagy [10]

Apoptin

• The chicken anemia virus derived protein
• Harbors cancer-selective cell killing characteristics
• Enhanced the oncolytic potential of adenovirus, parvovirus and Newcastle disease virus vectors [11]
• Intratumoral injection of attenuated Salmonella typhimurium bacterial strains and plasmid-based systems expressing apoptin
• Resulted in significant tumor regression [11]

Ganetespib

• Second-generation HSP90 inhibitor in GC treatment
• Reduced the growth of MGC-803 [96]
• Significantly inhibited the growth of SGC-7901 and MKN-28 in a dose-dependent manner [96]
• Induced G2/M cell-cycle arrest and apoptosis in all three cell lines [96]
• Caused pronounced decrease of expression of classic HSP90 client proteins [96]
• Greatly affected epidermal growth factor receptor (EGFR) signaling cascades [96]
• Decreasing the levels of total EGFR and EGFR on cell membranes [96]
• EGFR knockdown also induced cell-cycle arrest and apoptosis accompanied with a decrease of several EGFR downstream proteins [96]
• Responses of GC cell lines to ganetespib correlated well with their EGFR expression levels [96]
• Ganetespib worked synergistically with: [96]
• Radiation [96]
• Cisplatin [96]
• Inhibited the growth of xenograft tumors in vivo as a single agent or in combination with cisplatin [96]
• New potent treatment option