A class of compounds useful in pharmaceutical compositions and methods for treating or preventing cancer is described. The compounds' ability to inhibit RET kinase is quantified, i.e., their respective RET IC50 and EC50 values are described. One such compound, known as cyclobenzaprine and herein as SW-01, has been identified as RET-specific with an IC50 of 300 nM. SW-01 inhibits RET autophosphorylation and blocks the growth and transformation of thyroid cancer cell lines. It has been further tested in pancreatic cancer, breast cancer, and SCLC cell lines. The compounds show utility for inhibition of survival and proliferation of tumour cells.
Pharmacoproteomics Platform Identifying Kinome Features Regulating Drug Response In Cancer
The disclosure provides methods and compositions for increasing sensitivity, or decreasing resistance, of cancer cells to chemotherapeutic agents such as kinase inhibitor agents. In some embodiments, the cancer cells are hepatocellular carcinoma (HCC) cells. The methods and compositions can be integrated into methods of treatment of a subject with cancer, which can further comprise administering a chemotherapeutic agent such as kinase inhibitor agents. In another aspect, the disclosure provides a method for profiling the kinome of a cell or group of similar cells that incorporates kinase capture reagents and mass spectrometry analysis.
Frizzled 2 As A Target For Therapeutic Antibodies In The Treatment Of Cancer
Taranjit S. Gujral - Brookline MA, US Gavin MacBeath - Wakefield MA, US
Assignee:
PRESIDENT AND FELLOWS OF HARVARD COLLEGE - Cambridge MA
International Classification:
C07K 16/28
US Classification:
4241331, 4241301, 4241431, 4241391
Abstract:
Disclosed herein are methods of treating cancer in a subject, and methods for inhibiting growth, migration and/or invasion of a cancer cell in the subject, comprising administering to the subject a therapeutically effective amount of an antibody or antigen binding fragment thereof that downmodulates Fzd2. The antibody may specifically bind Fzd2, and may promote internalization of the Fzd2 receptor by the cancer cells and/or prevent ligand binding to Fzd2. Specific antibodies, and also specific portions of the Fzd2 molecule for antibody binding are disclosed. In one embodiment the antibody specifically binds to the epitope HGAEQICVGQNHSEDGAPAL (SEQ ID NO: 1). Specific cancers (e.g. late stage hepatocellular carcinoma), intended for treatment are provided, and include cancers that exhibit overexpression of Fzd2, and/or Wnt5a.