MARP 2023: Patti and David

Patti Kellerhouse, Advocate and David Freeman, Researcher

Patti Kellerhouse (Advocate)

I was super excited to attend the 10th Metastatic Breast Cancer Research Conferencre (MBCRC) and to be selected into the novel advocate/researcher program MBCRC Advocate Researcher Program (MARP).

This unique program was unlike most advocate programs where the advocates spend their time in one part of the meeting and the researchers in another (with minimal interactions between the two groups). This meeting was an intimate setting, with greater chance and purposeful scheduling of patients living with MBC and researchers to be interactive. Additionally, and most reflective, was the pairing of an advocate and researcher to learn about each other’s background with the idea that the two could share mutual future goals!

When I met my researcher, David Freeman (in the  MD/PhD program at the University of Utah),  I felt an instant connection (having collaborated with a veterinarian with the same name). I am now retired after being on long term disability with my Metastatic Breast Cancer. But I had a lifetime career in pre-clinical veterinary and human health research (pain, toxicology, animal science) and then my last ten years were in clinical cancer research. While preparing to celebrate my 9-year anniversary of early-stage breast cancer, on Oct. 2017 on my 60th birthday, I was diagnosed with MBC (5 liver lesions). This was while I was working on the Monarch clinical trials (my job as a Clinical Development Consultant (CDC) consisted of finding oncologists from sites on the west coast who wished to participate). These trials were imperative for FDA approval of Verzenio (abemaciclib) a CDK4/6 inhibitor, which ironically happened the same month (Oct2017) of my new diagnosis. After undergoing treatment with Verzenio plus standard of care (SOC), my liver lesions PET scan results were undetectable (No evidence of disease (NED)) before my second year of treatment. I continue  this first line of treatment today. So lucky to be alive, research is the main reason I can write this blog today.

It was so impressive to hear about David and his lab’s research. His poster entitled “CRIPTO regulated extracellular-vesicles activate breast cancer associate fibroblast” hypothesizes that CRIPTO promotes tumor plasticity by regulating fibroblast crosstalk in the local tumor environment.

Questions for David Freeman (Researcher):

1) What led you to study CRIPTO? The poster states that this protein regulates stem cells during development but disappears during adulthood. But reemerges during cancer and wound healing. What similarities are there with the cancer setting and wound healing?  

Some of the most aggressive breast cancer subtypes co-opt important developmental signaling pathways that are typically quiescent in adult tissues. To that end, our lab is interested in identifying important proteins in early mammary development as these may play important roles in tumors. We characterized the role for Cripto in promoting stem cell activity in developing mouse mammary glands which led us to investigate its role in breast cancer.

Much like how cancers co-opt developmental processes, tumors also exploit other signaling paradigms. Wound healing is a great example as it necessitates the production of numerous growth factors to facilitate cell proliferation and tissue repair. Tumors have for a long time been considered ‘wounds that don’t heal’. By mimicking a wound, the microenvironment surrounding the tumor starts producing these growth factors which act as fuel for the tumor.

2) These experiments have focused on TNBC. Do you think that your hypothesis will be similar for other BC subtypes, and will you be doing more work to prove this?

Absolutely! Breast cancer research is often focused on specific subtypes, but it’s likely that there are many mechanisms that are shared amongst subtypes that may prove to be effective therapeutic targets. Our current research is focused on TNBC because we see an enrichment in Cripto activity in TNBC samples. However, we are excited to expand this to other subtypes, including Her2+ tumors as Cripto has been implicated in Her2 signaling in previous work.

3) When I made my career change and decided to “get out of the lab” from pre-clinical to clinical research, it was not an easy task. The clinical side said I had no experience and I always thought well that makes no sense after approximately 30 years of preclinical research. As you mentioned you wish to bridge this gap. The two worlds are different, but skills learned in both are not. Especially since both pre-clinical and clinical are needed to succeed in our mutual goals. How can we change this stigma to increase our chances towards a cure for cancer?

It's a great question and one I think poses a major roadblock to promoting scientific progress from the bench to bedside (and back again). Both clinical and basic research carry immense complexities unique to their side and it’s not always easy to communicate or understand the barriers that the other side faces. Physician-scientists are one way to bridge this gap, but it takes a long time to finish that training and there are too few physician-scientists that are active in both research and clinic. I think promoting institutes, like many of the National Comprehensive Cancer Centers, that house research and clinic within the same building helps facilitate the interactions between clinicians and researchers is a great step forward. Just like advocates are becoming integrated into research discussions there needs to be an equal push to continue to embed clinicians within research groups (and vice versa).

4) One thing I remember from doing research is that each experiment creates even more questions. How new information gained from each laborious task leads to changes from what we first believed to be true. I feel that having advocates involved in the day-to-day activities of research will lead to a better understanding of the challenges researchers face and why it takes so long to get to even a publication besides a cure.  In which way do you think it is best to utilize advocates in your research?

It's a great point and it goes both ways. Having advocates involved in research can offer a perspective for advocates to understand why research can seemingly move so slowly from the outside. On the flip side, a lot of research often starts from a clinical question but as you mentioned the actual experiments are far from a linear path and it can be easy to wander off on tangential questions that while may be interesting, may not be the most clinically impactful. Having advocates involved in research not only helps with the initial question, but can help with all the intermediate decision points to keep the science pointed in a direction that will have an impact for patients.

David Freeman (Researcher)

For me, the 10th year of the Metastatic Breast Cancer Research Conference (MBCRC) marked a notable transition into how advocates and researchers could be integrated equally into scientific meetings. The initiation of the MBCRC Advocate Research Program (MARP) offered a unique blend of patient advocacy and scientific research collaboration, establishing a fresh avenue for building enduring relationships between advocates and researchers.  

My partnership with Patti Kellerhouse was a pivotal aspect of this conference. Patti, a retired professional with extensive research experience, brought her firsthand MBC diagnosis and strong advocacy background into our partnership. When I applied for MARP, I wrote about how my interest in pursuing an MD/PhD is to bridge the gap between basic research and clinical practice. It was fitting to be paired with Patti who occupies a unique position to blend scientific and advocate communities as both a researcher and an advocate herself.  

My current research is focused on unraveling the mechanisms by which tumors co-opt healthy tissue to promote tumor growth and disease progression. Specifically, I investigate the role of fibroblasts, a cell type typically involved in normal wound healing, in promoting metastatic disease. Ultimately, identifying unique signaling pathways required for crosstalk between tumor cells and fibroblasts may reveal novel therapeutic targets for disrupting the tumor microenvironment that cultivates aggressive tumor behavior.  

Despite coming from different scientific backgrounds, our strong passion for research formed the foundation of fascinating discussions ranging from alternative models of breast cancer, to the role of PAM50 subtypes in clinical decision making. It was a pleasure to get to know Patti at the conference and continue to learn more about her journey since then.  

Questions for Patti Kellerhouse (Advocate):  

1) You have been involved with the Congressionally Directed Medical Research Program as an advocate reviewer for 10 years now. Have you noticed a shift in how advocates are included in grants during this time? How has this experience shaped your own advocacy?

Yes, I do see a shift towards more advocates being involved in grants over the years. When I first started for the Department of Defense Breast Cancer Research Program (DOD BCRP) in 2013, I was so impressed by the whole idea. It was interesting to note that these grants which promote innovative models of research were spearheaded by the National Breast Cancer Coalition (NBCC) a grassroots organization. This experience has shaped my advocacy by making me understand that I represent many breast cancer patients from my community, and I must leave my personal opinions alone to represent them.

2) Having completed the National Breast Cancer Coalition's Project LEAD® Institute, you gained an educated advocate perspective. How have these skills influenced your approach to advocating for breast cancer patients, and what are some specific advocacy initiatives or projects you've been involved in as a result?  

What a great comprehensive refreshing training! Project lead introduced me to the policy end of advocacy. I abhorred politics in general but realized through attending their new Public Policy Academy that it is so important not only to understand research, but we need to change or create new laws that help patients get through a breast cancer journey. I had the chance to “go to the hill” and advocate for the Metastatic Breast Cancer Access to Care Act which if voted into congress will alleviate the extensive waiting period for social security and Medicare benefits. Many MBC patients die before they even get the benefits.

3) You have had a unique journey having been a CDC for the Monarch trials and then later initiating that same therapy (Verzenio). How has your previous research experience influenced your care as a patient with MBC?  

After reading my pet scan results revealing liver metastasis, prior to my oncologist appointment, I was prepared with a slide presentation to my oncologist (and family) as to why I wanted to take Verzenio.  One of the greatest attributes I say about my oncologist is that she really listens to her patients. That is so important. I guess my background prepared me to advocate for myself and to this day that is what I preach to others with the same disease.

4) With your background in research and advocacy, you're uniquely positioned to understand the importance of clinical trials in advancing cancer treatment. What message or advice would you give to MBC patients considering participation in clinical trials, based on your dual perspective as an advocate and a researcher?  

I always suggest at least considering a clinical trial. As an advocate (and a previous clinical trial participant) I help patients find trials through various programs such as MBC Alliance.  Then I encourage them if interested to discuss this with their oncologist. Many don’t understand the difference between cancer clinical trials and other disease clinical trials. I try to educate them on these differences and what questions to ask if they decide to proceed, for example “does your trial offer travel reimbursement for those living far away.”