In the Lab

On Cancer: Prostate Cancer Organoids Provide New Tool for Evaluating Therapies

By Julie Grisham, MS, Science Writer/Editor  |  Thursday, September 4, 2014
Stained pathology slides of a patient’s tumor (right) and of an organoid made from that tumor (left). Stained pathology slides of a patient’s tumor (right) and of an organoid made from that tumor (left).

An international team of researchers led by Memorial Sloan Kettering has created a new tool that can be employed in the search for personalized cancer therapies in prostate cancer: tiny formations called organoids. The study of organoids — three-dimensional structures about a millimeter in size composed of cells grouped together and spatially arranged like an organ or tissue — is a rapidly growing field in biology.

Traditionally, cell lines have been one of the main resources for evaluating potential new cancer drugs in the lab. Cell lines are populations of cells derived from a patient — such as a cancer cell — that can be grown indefinitely in culture.

“Identifying the molecular biomarkers that indicate whether a drug will work or why a drug stops working is paramount for the precision treatment of cancer,” says Yu Chen, the study’s senior author and a physician-scientist in MSK’s Genitourinary Oncology Service and our Human Oncology and Pathogenesis Program (HOPP). “By developing these organoids from patient prostate cancer samples, we are able to study the tumors in greater detail and correlate the genetic mutations with the response to various drugs.”

Organoids are also expected to provide much more information than cell lines. Because organoids mimic the structure of tumor tissue, they will enable the study of how the cancer cells interact with each other and the effect of hormones on tumor growth, for example, in addition to providing genetic markers for targeted drug therapies.

A Need for Better Prostate Cancer Models

Despite prostate being the most common type of cancer in men after skin cancer, until now there have been only a handful of prostate cancer cell lines available for testing of new drugs. “Many of the mutations that cause prostate cancer occur in a small percentage of patients and are not represented at all in the cell lines currently available,” Dr. Chen explains. “And with so few lines, we haven’t had the statistical power to properly evaluate targeted therapies that may act against these mutations.”

In the new study, published in Cell, the researchers reported successfully growing organoids from the tumors of seven patients with metastatic prostate cancer. Each three-dimensional organoid is molecularly identical to the patient’s cancer from which it originated. With the addition of the seven organoid lines described in this paper, Dr. Chen’s team has effectively doubled the resources available for doing this kind of testing of new prostate cancer drugs.

A New Era of Personalized Medicine

The organoids are proving useful in learning more about the effectiveness of current and experimental prostate cancer therapies. The prostate cancer organoids can be used to test multiple drugs simultaneously, through a technique called high-throughput screening.

Eventually, the researchers say, they may be able to develop organoids that are derived from each patient’s tumor, allowing drugs to be tested on the organoid before being given to the patient to truly personalize and optimize each person’s treatment. Dr. Chen’s team is already retrospectively comparing the drugs given to each patient against the organoids for clues about why the patient did or didn’t respond to therapy.

An Exploding Field

The use of organoids in studying cancer is relatively new, but the field is exploding quickly, according to Dr. Chen. In 2009, Hans Clevers, a researcher at the Hubrecht Institute in the Netherlands, first demonstrated that intestinal stem cells could form organoids. Dr. Clevers is a co-author on the Cell study, along with HOPP Chair Charles Sawyers, Genitourinary Oncology Service Chief Howard Scher, and many other members of MSK’s prostate cancer team.

Organoids derived from patient tumor samples, sometimes also called tumoroids, are being studied at Memorial Sloan Kettering and elsewhere for many other tumor types, including kidney, pancreas, and thyroid.

Watch a video of Dr. Chen discussing his research on Yahoo! News.

Funding for this research was provided by the Prostate Cancer Foundation, the Movember Foundation, the Geoffrey Beene Cancer Center, the Starr Cancer Consortium, the US Department of Defense, and the National Institutes of Health under grants 5K08CA140946, P50CA092629, CA155169-01A1, and 5R01CA116337. It was also funded by a Stand Up To Cancer Dream Team project grant.

Comments

My husband undergone a radical prostatectomy on 06/10/2013 for Adenocarcinoma of the prostate with a pathology report of pT2c , pNx , pMn/a. Gleason scores 7 (3+4) and 8 and PSA level 10ng/ml and with perineural invasion present.
But, his PSA levels went from 0.18 on the third month follow up to 0.4 on the 9TH after the surgery.
So, the doctors told us that he would have good chance with salvage XRT. Facing the side effects after the XRT treatment, we decided to go for PROTON radiation therapy which was prescribed 39 treatments that my husband has just finished.
Because no CT scan nor bone scan were taken before starting the treatment, I am wondering if the treatment with the ADT and Proton would be a better choice because his father passed way from adenocarcinoma at age 69.
Could you please advise me on that?
Thank you

Unfortunately, we are unable to answer specific medical questions on our blog. If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at 800-525-2225 or go to http://www.mskcc.org/cancer-care/appointment.

I have prostate cancer and have had radiation treatment. I am taking meds of 3month intervals of shots of hormone in my stomach along with Biculamide. I am eating much greens for food and drinking a "power smoothie" that my wife makes each morning with kale, baby spinach, and some minimal fruit. I am also drinking a Vitamin C drink( 1 to 1 1/2 oz twice a day) made with Pharmceutical grade Vitamin C and encapsulated in Sunflower Lecithin. I mix it in a Sonic chamber for 15 min to encapulate it. My psa originally was 30 then to 45 and now it is .5. What is your medical opinion of using Vitamin C theraphy and do you do it? I would do the intravenous if I could find it economically as I live off my SSI. Please reply what your research has shown about Vitamin C fighting cancer. See also Univ. of Kansas Medical Ctr for Vit C intravenous theraphy.

Mr. Moberg, thank you for your comment. You can read about what research has shown so far about vitamin C therapy at this link:

http://www.mskcc.org/cancer-care/herb/vitamin-c

There also is information from the National Cancer Institute at this link:

http://www.cancer.gov/cancertopics/pdq/cam/highdosevitaminc/patient/page2

In addition, our Integrative Medicine Service, which maintains the "About Herbs" database that includes the information about vitamin C, offers nutritional counseling (for a fee) and can answer any additional questions you may have on this topic. Below is the link and phone number if you want to call to make an appointment for a consultation.

http://www.mskcc.org/cancer-care/integrative-medicine/individual-therapies

Phone: 646-888-0800

Dr Chen Is My Medical Oncologist At MSK And I Am Proud To Say In Addition To Be Researching These Organoids He Is An Excellent , Caring And Highly Professional Physician . Can't Thank You Enough Dr Chen !

Hi there,

Great article. I am in third year university taking a Histology course and am using this article for a research paper. I have a question regarding the 2 histology sections above - what microscope magnification are they in?

Thanks,
Sage

Sage, we're glad you enjoyed the article. We forwarded your question to Dr. Chen, and he said that the images were taken with a 20x objective. Thank you for your comment.

Add a Comment

We welcome your questions and comments. Because this is a public forum, please do not include contact information or other personal details. Also, keep in mind that while we can provide general information and resources, we cannot offer personal medical advice. To make an appointment with one of our experts, contact our Physician Referral Service at 800-525-2225 or online.
Your e-mail address is kept private and will not be shown publicly.

More information about formatting options