The main reason why metastasis is so deadly is because it is frequently resistant to treatment. Researchers at the University of Chicago Ludwig Center are searching for new ways to take advantage of steroid hormones and their receptors to detect metastases and deliver treatments directly to tumor cells to inhibit cell growth or promote cell death.
Receptor-directed cancer therapy is ideal because steroid receptors provide highly specific and accessible targets even in metastatic cancer. Multiple human tumors, especially those of the reproductive tract, often express steroid receptors at high enough levels to allow targeting. For example, breast cancers express estrogen receptor (ER), and prostate cancers express androgen receptor (AR), both of which are widely used as therapeutic targets. Furthermore, it is possible to label receptor ligands with an atom that will allow imaging to determine whether the tumor contains sufficient levels of the receptor to be a target for therapy. Thus, one research aim is to develop and characterize radiolabeled selective steroid receptor modulators (SRMs) that can be used at any stage of tumor progression to image and kill tumor cells that express ER or AR. Investigators are initially targeting breast and prostate cancers, and also cancers of the ovary and lung.
A second aim of the Ludwig Center is to develop novel receptor-targeted nanoparticle reagents for cancer imaging and therapy. This aim represents a multidisciplinary collaboration to develop nanoscale materials that can be used to selectively and precisely image tumor cells as well as deliver therapy to a wide array of cancers at all stages of progression including metastasis. Researchers are initially targeting nanoparticles to the ER and AR in order to better understand the distribution of receptors and their signaling functions within cancer cells.
Metastatic tumors that respond initially to receptor-based therapies almost always become hormone-independent and resistant to therapy. Also, many cancers do not rely on hormones for growth. The main treatments for these tumors are chemotherapy and radiation, but the overall effectiveness is disappointing for metastatic disease. Investigators are searching for ways to improve these therapies by understanding how cancer becomes resistant to treatment. The third research aim of the Center is to identify and develop novel small molecules that will sensitize tumors to ionizing radiation and/or chemotherapy independent of hormone receptor function. Cancers of the breast, head and neck, lung, ovary and prostate are being targeted.