Molecular Differences Contribute to Disparity Between Black and White Patients with Prostate Cancer

Levels of cytochrome C, a protein produced with the mitochondria of cells, were significantly lower in Black patients compared with White patients with prostate cancer, according to Dhyan Chandra, PhD.

This molecular difference added to the already existing health care disparities within the disease for different populations, Chandra added.

“Prostate cancer health disparity is real, and we need to go deeper [molecularly]. There are some studies that suggest if patients have equal resources, the disparity is not much there,” Chandra said. “But there are major molecular differences between these 2 populations, and we cannot be disregard that. We need to go deeper to understand so that we can remove this disparity between different populations.”

In an interview with OncLive^®, Chandra, associate professor of oncology in the Department of Pharmacology and Therapeutics, member of the PhD Program in Cancer Sciences, Experimental Therapeutics Track, member of the Developmental Therapeutics of Comprehensive Cancer Center Support Grant Program, member of Breast, Lung, Genitourinary, and Gastrointestinal Translational Research Groups, at the Roswell Park Comprehensive Cancer Center, discussed recent findings relating to low levels of cytochrome C in Black men with prostate cancer, plus plans for future research on this topic.

OncLive^®: Can you expand on the research you will be conducting to help address disparities in prostate cancer?

Chandra: I have been [studying] prostate cancer health disparities for some time. In the past 7 or 8 years, we have made a lot of progress in this field, especially focusing on the difference between African American and Caucasian American [patients]. [This is specifically] in terms of the molecular aspects because the differences between prostate cancer health disparities are multifactorial, so it's not 1 thing. But how the biology differs between these 2 population groups is not known.

We began investigating on this topic, and the first thing we found [was] that mitochondria, one of the organelles within cells, is highly defective in African American patients with prostate cancer, compared [with] Caucasian American patients with prostate cancer. Based on that, we dug deeper on this topic and found that this is the case.

We found that 1 of the proteins in mitochondria is called cytochrome C. Cytochrome C is very important protein that participates in energy production. Most of the cells need energy to survive, so this is 1 of the proteins that participates in energy production. But it turns out this protein, when released from mitochondria, induced apoptosis, which is a cell death program. That means it had 2 functions. One is to get energy for themselves, and the other was to induce cell death.

We found that in African American patients with prostate cancer, the cells have a low level of cytochrome C. Our grant is based in this finding we published in cancer research. Our goal is to understand how we can restore cytochrome C. This project that is funded from the American Cancer Society is to develop different approaches so we can restore mitochondria cytochrome C, so we can restore mitochondrial function, and cell-death inducing function of mitochondria.

What is your end goal?

Our goal is to go find the best combination therapy that will induce the level of the cytochrome C in prostate cancer cells derived from African American [patients]. That will allow us to find approaches so that we can go to clinical trial and induce cytochrome C production in prostate cancer cells in African American patients so we can get better mitochondria function, inducing more cell death in prostate cancer.

Are other groups investigating mitochondria function in this setting?

I see that this is a very interesting field now. I don't believe there's any clinical trial that is specific to these prostate cancer health disparities, because a lot of time, people still don't know the best region for this, especially the molecular region for prostate cancer health disparities. We are one of the few focusing on how mitochondria are important for addressing prostate cancer health disparities.

What other steps are necessary to help close the gap in disparities and ensure molecular differences are being addressed?

When a patient comes to the clinic—Caucasian American, African American, any kind patient—we need to understand whether the mitochondria is functional. That’s one of the things that we don’t have in clinic. A lot of the things that they have, maybe genomic analysis, they [test for] the known gene mutations. But they [do not] know enough.

Not [many] initiatives have been considered in terms of whether mitochondria are functional or not. We found that mitochondria are not very functional in African American patients with prostate cancer. This can be 1 of the strategies that can be adopted to see whether the mitochondria do not need too much work, and western blots to see the level of cytochrome C.

If you feel that they have a low level of cytochrome C, that means the therapy may not work. For that reason, it is important to understand whether the patient [has detectable levels of] cytochrome C and see whether the mitochondria is functional to induce cell death in prostate cancer. That 1 thing to suggest is something that in the future that can be a strategy to adopt.

What would be an overall message regarding prostate cancer disparities that you’d like to share with colleagues?

Prostate cancer health disparity is real, and we need to go deeper [molecularly]. There are some studies that suggest if patients have equal resources, the disparity is not much there. But there are major molecular differences between these 2 populations, and we cannot be disregard that. We need to go deeper to understand so that we can remove this disparity between different populations.

Is there anything else you want to highlight?

There is a lot of interest in this field, but resources are limited. If we have more resources that can be provided to people, especially those who are working, so that can take the findings that we have [to different levels]. If they have found some differences, they can take this initiative so that we can make faster progress in this field.

Even though we have more resources available than before, it’s important to think about a broader perspective. [For example, in] Caucasian American patient population cohorts, some patients may have a similar characteristic as African American [patients], so it will be beneficial for all population groups. But it's more beneficial for African American [patients], especially from the mitochondrial dysfunction point of view.