Monoclonal Antibodies for the Treatment of Cancer.

The ability of cancer cells to evade the immune system is one of the most deadly characteristics of the majority of malignant tumours. Accordingly, the recent development of antibodies which target tumor cell evasion of immune checkpoints such as the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) as well as the programmed cell death protein (PD-1) and the PD-1 ligand (PD-L1) has been a major and apparently highly effective approach in the treatment and/or eradication of a variety of highly malignant forms of cancers. The US Food and Drug Administration (FDA) has recently approved the application of lpilimumab (which targets CTLA-4) and pembrolizumab (targeting PD-1) for the treatment of advanced gastric cancer.

Oncolytic potential of a novel KGFR tyrosine kinase inhibitor using a KGFR-selective breast cancer xenograft model.

Background: Keratinocyte growth factor (KGF)/KGF receptor (KGFR) signaling produces a rapid increase in the progression of breast cancer. Molecular modeling was used to create a group of KGFR-selective kinase inhibitors (TKI). Compound L-27 is a potent and selective KGFR TKI.

Synthesis and in vivo evaluation of N-ethylamino-2-oxo-1,2-dihydro-quinoline-3-carboxamide for inhibition of intestinal tumorigenesis in APC(Min/+) mice.

A selective KGFR tyrosine kinase inhibitor, N-ethylamino-2-oxo-1,2-dihydro-quinoline-3-carboxamide, was synthesized and its possible inhibitory effects on the development of colon polyps and colorectal tumors was examined in APC(Min/+) mice, a mouse model of human intestinal familial adenomatous polyposis. The present study shows for the first time that a dietary administration of a selective KGFR tyrosine kinase inhibitor lacks the overt-toxicities and significantly reduced the growth of small intestinal polyps in both male and female APC(Min/+) mice. This inhibition of polyp growth appears to occur at a greater extent in female mice.

Influence of novel KGFR tyrosine kinase inhibitors on KGF-mediated proliferation of breast cancer.

Background: Keratinocyte growth factor (KGF) acts at the KGF receptor (KGFR) to produce a rapid stimulation of breast cancer cell proliferation and motility which is mediated via the Erk signaling pathway. Enhancement of KGF/KGFR signal transduction may be an early step in the metastatic progression of breast cancer. Receptor modeling of KGFR was used to identify selective KGFR tyrosine kinase (TK) inhibitor molecules that have the potential to bind selectively to the KGFR.

Selective growth inhibition of cancer cells by L-methioninase-containing fusion protein targeted to the urokinase receptor.

Background: We have reported the development of a novel fusion protein (FP) consisting of an amino-terminal fragment of urokinase linked to the amino terminus of the enzyme L-methioninase (L-M). The present study compared the effect of this novel FP on the proliferation of human ovarian, skin, breast endometrial and pancreatic cancer cell lines.

Methods: The FP, L-M and a mutated FP, with reduced L-M activity, were produced by recombinant methods.