AACR 2017: Organoids & Neuroendocrine Prostate Cancer

nepc organoidsAt the American Association for Cancer Research (AACR) 2017 Annual Meeting, researchers and physicians from Weill Cornell Medicine and NewYork-Presbyterian presented updates on the use of organoids in neuroendocrine prostate cancer.

Dr. Mark Rubin, Director of the Englander Institute for Precision Medicine, spoke about functional testing to use organoids to determine drug sensitivity or resistance. We have previously shown the power of sophisticated genomic analysis, but the information obtained by extracting DNA or RNA from a sample is fixed in time. Organoids allow for testing of many different types of tumor processes or properties, including the examination of important cellular pathways and treatment sensitivity and resistance. For example, we can test certain drugs or drug combinations to see how well they work or don’t work on a specific tumor or tumor type. For instance, in a clinical trial to examine the response of men with neuroendocrine prostate cancer (NEPC) to a drug called alisertib, we took tissue biopsies before the patients started treatment. From these tissues, we developed organoids. We then used these organoids to test response to alisertib. Treating the organoids with the drug showed the same results as in the patients (one with an exceptional response and the other with treatment resistance).

LoredanaLoredana Puca, PhD, a postdoctoral associate mentored by Drs. Beltran and Rubin, highlighted the similarities in the microscopic anatomy of the cells and tissues (also referred to as the histology) between the organoids and the original biopsy tissue at the 2017 AACR meeting. Additionally, she presented results showing how the tumor’s DNA (also referred to as the genomics), as well as way the cells encode RNA to create proteins (also referred to as transcriptomics) – both of which are integral to the tumor’s ability to grow and mutate – are similar between organoids and biopsy. This sets the stage to utilize organoids for diagnostic and treatment testing in the hopes that the results will be more analogous to human tumors than traditional cell-line work.

Learn more about this research by visiting Dr. Beltran’s lab website. For additional information about organoids and how they work check out this recent blog post.

Mini Organs: What Organoids Can Tell Us

Historically, cancer research has been conducted using cell lines that grow in a petri dish. We’ve been able to learn a lot and make much progress in the fight against cancer using this approach, but it also has some limitations, as the environment is not truly reflective of the way cancer cells grow and metastasize within the human body – a three-dimensional (3-D) environment. Additionally, cell lines can mutate over time and then sometimes no longer reflect the genetic and molecular variants of cancer cells.

Over the past 10-15 years, medical research has evolved and grown (literally and figuratively) – what used to only be possible in sci-fi movies and imaginations is now a reality as we create mini-models of bodily organs in the laboratory. These 3-D structures are also known as organoids, and an exciting area of this research is related to cancerous tumors.

Cancer biopsies remove tumor cells directly from the body. Often these biopsies are conducted when a primary tumor is found and removed, and sometimes also if the cancer has grown and spread to other locations throughout the body. This is because tumor cells evolve and change over time, especially as they try to develop workarounds in response to treatment. From the tumor cells that are removed in a biopsy, we’re analyzing the pathology and learning about the cancer on the molecular and genetic level, including any mutations we may be able to target.

Another way we’re able to use these tumor cells is to grow organoids in order to replicate the tumor outside of the body. This 3-D representation of the tumor allows us to conduct research in a way that better addresses the complex structure of the cancer. It is a form of precision medicine or personalized medicine, and allows us to test how an individual patient’s cancer cells may respond to a wide range of treatments.

This video created by the Englander Institute for Precision Medicine provides an overview of how this process works: