Transferrin Receptor Identifies a Comprehensive Pool of Circulating Tumor Cells with Unique Molecular Features from Metastatic Prostate Cancer Patients
Abstract
Prostate cancer (PC) disease affects more than 2 million men in the United States. The growth of PC and of the castration-resistant version of PC (called CRPC) heavily relies on androgen hormones such as testosterone. Thus, an effective approach to suppress prostate cancer has been to treat patients with agents that block testosterone (drugs like abiraterone and enzalutamide). However, many patients fail to respond to hormone therapy and eventually progress to a lethal type of PC, called neuroendocrine prostate cancer (NEPC). Chemotherapy is the only effective treatment for these patients and provides a significant survival benefit. Unfortunately, some patients will not benefit at all or will stop benefiting from chemotherapy and their disease will progress. One of the biggest goals in oncology is to understand why, in some patients, chemotherapy stops working and, in others, doesn’t work at all. This knowledge will allow us to design more effective therapies: we would treat patients with the right drug, avoiding the ones that wouldn’t work. To this end, taking a piece of the tumor from the patient (biopsy) and studying it can be useful. Unfortunately, we will need to extract several pieces from different sites of the tumor at different times to effectively study the disease. Biopsy is a very painful process and, in some cases, dangerous. Alternatively, cancer cells can be found in the blood of patients (circulating tumor cells [CTCs]) after they leave the tumor and use the blood to move to other parts of the body. Unfortunately, these cells are rare and difficult to find; moreover, the current method to isolate CTCs is very inefficient, as it misses the majority of the cells. Our research group has unique expertise in capturing and analyzing these cells. We recently identified a novel role for an already known molecule, called Transferrin receptor, or TfR, that can help us find these elusive CTCs. TfR usually helps cells catch the iron they need to live. We found out that TfR extensively marks the majority of prostate cancer cells. Our preliminary experience showed us that TfR finds many more CTCs than the usually employed method. In this project, we plan to use TfR as an innovative way to identify the CTCs that otherwise would stay unnoticed in prostate cancer patients. This unprecedented approach to find CTCs will allow us to fully use CTCs as a sort of “liquid biopsy” to know the crucial genetic features of the patient—all this only through a simple blood draw. Our goal is to use the information on the tumor features obtained by CTC analysis to understand whether the treatment will be effective for the patient before starting the treatment. We believe that monitoring the expression of certain genetic features associated with good response or resistance to prostate cancer treatment will enable us to predict in advance the efficiency of the treatment. For this reason, we will look into the genetic characteristics of the CTCs before starting the treatment, during the treatment, and at the end of it, aiming to identify genetic changes that we could associate with the treatment’s efficiency or failure. Our ultimate goal is to foresee whether the treatment works so we can ultimately choose the right drug for each patient, avoiding unnecessary drug toxicity and loss of valuable time following an inefficient therapeutic path. Overall, this project could establish an efficient and fast manner to direct patients to the right treatment and ultimately save more lives.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910666
Entities
People
- Paraskevi Giannakakou
Organizations
- United States Army
- Weill Cornell Medicine