Reinventing the wheel

Dr. Weeks’ Comment:     Here (finally!)  is some research accomplished in 2009 which supports the clinical practice of IPT which was called quackery in 1940. It demonstrates that the IGF-1 receptor is the back door, unguarded, which we can use to bring chemo drugs preferentially into the cancer cell.   Elegant research in 2009; stupendous clinical work in 1940.

Lucky they who listened to Dr. Perez Garcia and didn’t wait around for the experts to endorse the work.



Transl Res. 2009 Jun;153(6):275-82. Epub 2009 Mar 14.

Novel insulin-like growth factor-

methotrexate covalent conjugate

inhibits tumor growth in vivo at lower

dosage than methotrexate alone.


McTavish H, Griffin RJ, Terai K, Dudek AZ.

IGF Oncology, LLC, Saint Paul, MN 55110, USA.



The insulin-like growth factor receptor is overexpressed on many types of cancer cells and has been implicated in metastasis and resistance to apoptosis. We report here the development of a novel covalent conjugate that contains the antifolate drug methotrexate coupled to an engineered variant of insulin-like growth factor-1 (IGF-1), long-R3-IGF-1, which was designed to target methotrexate to tumor cells that overexpress the membrane IGF-1 receptor. The IGF-methotrexate conjugate was found to contain at least 4 methotrexate molecules per IGF-1 protein. The IGF-methotrexate conjugate bound to MCF7 breast cancer cells with greater than 3.3-fold higher affinity than unconjugated long-R3-IGF-1 in a competition binding assay against radiolabeled wild-type IGF-1. Compared with free methotrexate, the IGF-methotrexate conjugate required slightly higher concentrations to inhibit the in vitro growth of the human prostate cancer cell line LNCaP. In vivo, however, in a mouse xenograft model using LNCaP cells, the IGF-methotrexate conjugate was more effective than free methotrexate even at a 6.25-fold lower molar dosage. Similarly, MCF7 xenografts were inhibited more effectively by the IGF-methotrexate conjugate than free methotrexate, even at a 4-fold lower molar dosage. Our results suggest that the targeting of the IGF receptor on tumor cells and tumor-related tissues with IGF-chemotherapy conjugates may substantially increase the specific drug localization and therapeutic effect in the tumor.

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