|United States Of America||Issued Patent||9,909,128||03/06/2018||2012-794|
Breast cancer is the most widely-diagnosed cancer in women. Over 266,000 women in the US will be diagnosed with breast cancer this year. Approximately 95% of breast cancers express prolactin receptors compared to 70% of breast cancers that express estrogen receptors. It is desirable to develop a therapy to target a common receptor expressed in ~95% of breast cancers.
UCR researchers have designed novel splice modulating oligonucleotides (SMOs) that decrease expression of the long form of the prolactin receptor, thereby significantly inhibiting the metastatic spread of breast cancer to the lungs and liver. The SMO treatment also increased central death in the primary breast tumor. These SMOs may also target metastases produced by non-prolactin receptor-expressing primary tumors since all cancer stem cells examined so far are positive for the prolactin receptor. The researchers administered SMOs to two highly aggressive metastatic models of breast cancer, BT474 human xenografts, used for testing Herceptin, and a 4T1 syngeneic mouse model, which allows testing with an intact immune system.
Fig. A shows a reduction in the number of metastatic colonies upon treatment with the UCR SMOs.
Fig. B titled "Control" is a stain of the metastatic colonies without SMO treatment. Fig. B titled "PRLR SMO" is a stain of the colonies after 40 days treatment with the UCR SMOs.
breast cancer, metastasis, cancer stem cells, splice modulating oligonucleotides, SMO, prolactin receptor, alternative splicing, splice isoform, therapeutic, kinase phosphorylation