Metastasis, the deadliest aspect of cancer, is notoriously resistant to treatment. The Ludwig Center is searching for new ways to take advantage of cutting-edge technologies to identify, characterize and target disseminated tumor cells, with the goal of eventually developing successful treatment or prevention strategies for metastasis. A current research focus is to target steroid hormone receptors to detect metastases and deliver treatment directly to tumor cells through the use of radiolabeled hormones.  This highly specific targeting holds great promise for the treatment of metastatic cancers of the breast, prostate, ovary and lung. The Ludwig Center is also investigating the mechanism of oligometastasis, an intermediate stage between localized and widespread disease. By understanding the origins and possible treatments of this stage of disease, we hope to further our knowledge of metastasis. These investigations also include studies of how microRNAs influence metastatic behavior and the immune activating effects of radiotherapy.

Receptor Targeted Radiotherapy

An important research goal of the Center is to develop and characterize novel steroid receptor modulators (SRMs) that can be used at any stage of tumor progression to image and kill tumor cells that express one or more members of the steroid receptor family, including the estrogen Receptor (ER), androgen Receptor (AR), and progesterone receptor (PR). Many human tumors, especially those of the male and female reproductive tract, express significant levels of two or more of these receptors, which makes them suitable for targeting, in contrast to existing therapies that rely on the use of single receptor antagonists or hormone deprivation to inhibit tumor cell proliferation and promote apoptosis. Because breast and prostate cancers express high levels of ER and AR respectively, our current focus is on these receptors and cancers as therapeutic targets. The Center is investigating the feasibility of labeling receptor ligands with a short-lived radioisotope to identify tumors that have sufficient levels of these receptors to be a target for intracellular radiotherapy with the same isotope. Initially, breast and prostate cancers will be studied, but this technique could also be applied to cancers of the ovary and lung. 

Tumor Targeted Nanoparticles

Additionally, the Ludwig Center aims to develop novel nanoparticle reagents for cancer imaging and therapy. This multidisciplinary initiative would create nanoscale materials with the ability to selectively and precisely image tumor cells, as well as deliver therapy to a wide array of cancers. Initially, researchers are targeting CD47-expressing breast cancer cells with microRNA-containing, self-assembling nanoparticles, to determine the feasibility of using this approach to deliver chemotherapy only to tumor cells.

Understanding and Treating Oligometastasis

Investigators at the Ludwig Center propose to discover the mechanism of and potential treatments for oligometastasis as a step toward understanding metastatic spread and identifying a substantial proportion of patients with this subset of metastasis. By understanding this stage of cancer spread, we hope to eventually find effective and safe treatments for different stages of metastasis.

Currently, one of the most promising treatments for oligometastasis is stereotactic body radiotherapy (SBRT), which allows for higher precision and higher doses of radiation than other externally delivered radiation technologies. The Ludwig Center has conducted several clinical trials of SBRT treatment on patients with metastases in multiple sites, with data suggesting that oligometastasis does in fact exist and that some patients may experience a survival benefit from SBRT or surgery. In the future, we hope to better identify the patients that may be benefited by this type of treatment. To this end we are studying a microRNA signature to identify these patients and gain further insights into the behavior of metastasis.  We are also investigating the basis of resistance to radiotherapy and chemotherapy through a newly identified pathway that involves genes that mediate the effects of interferons. These investigations are important because patients with oligometastasis are likely to receive both radiotherapy and chemotherapy.