Five questions for Dr. Xiaohong Li: Prostate cancer and bone metastasis

This month, men across the U.S. will amp up their moustache game to raise awareness of men’s health issues such as prostate cancer.

According to the National Cancer Institute, in 2017 alone, more than 161,000 men will be diagnosed with prostate cancer. The good news is that the five-year survival rates for the disease have been steadily increasing—up from 66 percent in the mid-1970s to 98.6 percent today, thanks to new detection methods and treatments.

However, despite the progress in detection, difficulties remain.  Although most prostate cancers are slow-growing (so much so that some may not ever require treatment), a subset of tumors can be aggressive. These fast-moving cases require quick and intensive treatment such as surgical removal of the prostate, which comes with its own set of risks and side effects.

Of great concern is that we still don’t have a good way, such as a blood test, to differentiate between a slow-growing prostate cancer and an aggressive one, thereby putting patients and their physicians in a difficult situation. These aggressive cases also tend to spread, particularly to the bones, where they become much more problematic to treat.

This spread or “metastasis” to the bones is exactly what Van Andel Research Institute scientist Dr. Xiaohong Li hopes to prevent. We asked Dr. Li five questions about her research into prostate cancer, bone metastasis, and where diagnostics and treatments are headed in the future.

Dr. Xiaohong Li

What does your lab study at Van Andel Research Institute?
We have two projects on prostate cancer research in the lab. One project is focused on prostate cancer bone metastasis—the spread of cancer to the bones—and the other one is focused on tumor dormancy.  Most scientists studying cancer are just looking at the cancer cells. I study the tumor microenvironment, which includes the cells around and inside a tumor mass.

We are looking at the tumor microenvironment to study the role the area around the tumor plays in the development of cancer. When we find some of the *stromal cells that stimulate the tumor growth, we try to identify the dysregulated cell signaling and then try to block them. A lot of therapies are available that target the cancer cells, so we want to find new ways to stop the helper cells around and in the tumor mass.

Why does prostate cancer metastasize to the bone?
There are a lot of hypotheses as to why prostate cancer cells metastasize or go to the bone, but there is no perfect explanation as to why. One thought is that bone marrow is rich in material like stem cells. We also know that bone contains a lot of hiding places for cancer cells.

How do prostate cancer cells hide in bone?
Cancer cells can hide in bone and attach to *osteoblast cells, and they sometimes become dormant and sleep. At some point, the dormant cells become awakened in the bone. Recently, there have been a few clinical trials that have used therapies to awaken the dormant cells, then target them with chemotherapy. That method is dangerous because you’re unleashing your enemies in order to attack them, and there is a chance that the cells you unleash will not be killed by the chemotherapy. So, in that regard, it’s very risky. We want to find ways to keep the cells dormant and maybe find a way to manage them like a chronic disease and, once we can do that, we want to find a way to destroy them while they are dormant.

Why is prostate cancer difficult to treat?
One of the reasons it is hard to treat is that prostate cancer cells are not highly proliferative. They are slow-growth cells, and sometimes they have a similar growth rate of normal cells. So, chemotherapy or other general use therapies that target fast-growing cancer cells aren’t effective against prostate cancer cells.

The first-line therapy for fighting prostate cancer is hormonal therapy. Prostate cancer cells depend on the male androgen hormone, and hormone therapy blocks the androgen receptors in cells. But the therapy is not perfect and it is almost guaranteed to induce drug resistance. Prostate cancer cells are always changing and adapting, and it makes treating the cells difficult. We are also studying how to overcome the drug resistance from targeting the tumor microenvironment.

What gives you hope regarding new diagnosis and treatment options for prostate cancer?
In the last few years we have made great strides in finding therapies that not only improve the quality of life for patients, but also increase survival rates in patients. Because of technological progress, we can now diagnose prostate cancer using a blood screen to find the circulating tumor cells in the blood. And there is also a lot of hope for combination therapies that might include chemotherapy, immunotherapy, hormone therapy and single-cell sequencing technology to develop personalized treatments that can extend life. There is still a lot of hope for where the future might lead, and we will continue to look for a curative treatment approach for prostate cancer.

*stromal cells = A type of cell that makes up certain types of connective tissue (supporting tissue that surrounds other tissues and organs).
*osteoblasts = A type of cell that creates bone by producing a matrix that then becomes mineralized. Bone mass is maintained by a balance between the activity of osteoblasts that form bone and cells called osteoclasts that break it down.