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Dr. Sonia del Rincón on SU2C Dream Team Grant Impact

Sonia del Rincón, PhD

Dr. Sonia del Rincón and the Stand Up to Cancer (SU2C) Canada Metastatic Breast Cancer Dream Team are looking to understand the impact of MAP kinase–interacting serine/threonine kinases 1 and 2 (MNK1/2) inhibitors on metastatic breast cancer. Completing her postdoctoral training focusing on identifying novel druggable targets in breast cancer at the Sanford Burnham Prebys Medical Discovery Institute, Dr. del Rincón serves as an Assistant Professor in the Department of Oncology at McGill University. As an Early Career Investigator researching alongside team Leader Dr. Nahum Sonenberg and Co-leader Dr. Michael N. Pollak, Dr. del Rincón offers her perspective on the impact of this SU2C Dream Team grant:

What inspired you to pursue metastatic breast cancer research?

Knowledge that 1/3 of women diagnosed with breast cancer will develop metastasis has always driven me to investigate strategies to block metastasis. These women could be our mom, sister, aunt, friend. Unfortunately, metastasis remains a significant unmet clinical challenge. My lab is dedicated in large part to understanding how breast cancers highjack signaling pathways as a means to acquire aggressive phenotypes leading to their increased metastatic potential.

In your view, what is the potential impact of the grant to the field, and what does it mean, for you, to be a part of a SU2C Dream Team grant?

Our SU2C Dream Team grant funds clinical testing of inhibitors of MNK1/2, regulators of protein synthesis, in women with metastatic breast cancer. My research program is particularly interested in the activity of MNK1/2, which we have shown are metastasis promoters and therapeutic drug targets (JCI 2017, Cancer Res 2019, Oncogene 2020). Our involvement in the SU2C Dream Team is an uplifting and unique opportunity for my entire research team. In particular, my trainees are excited that the work they are doing in pre-clinical mouse models of cancer and single-cell imaging of patient samples can potentially impact the clinical testing of MNK1/2 inhibitors.

What excites you about your research’s potential impact?

The fact that MNK1/2 inhibitors have emerged as druggable targets that are being tested in the clinic, encourages us to see the potential relevance of our discoveries at the bench to women diagnosed with metastatic breast cancer. We are using imaging mass cytometry (IMC), a state-of-the-art single-cell, highly multiplexed imaging technology, to examine in which cells MNK1/2 are most active. In doing so, we hope to elucidate previously unknown impacts of inhibiting these kinases in patients, with the goal of potentially discovering additional therapies that can be used in combination with MNK1/2 inhibitors.

In three sentences, how would you describe your research to a friend?

Protein synthesis is often hijacked in cancer cells that decide to spread throughout the body (i.e. metastasis). We study a pathway that controls such faulty protein synthesis and have shown that blocking it also blocks invasion and metastasis. Stand Up to Cancer has funded the clinical testing of drugs that block this faulty protein synthesis pathway in women with metastatic breast, and thus we will gain a better understanding of how these therapies work in patients with advanced cancer.

What do you consider the most important scientific advance(s) you hope to make because of your SU2C Dream Team Grant?

We have been studying the role of MNK1/2 in cancer for the past 5 years. We know that MNK1/2 have important roles in tumor cells, but also in tumor supportive cells of the microenvironment. With access to patient-derived tumor material from our SU2C Dream Team trial, we are uniquely positioned to image the changes that occur in response to MNK1/2 inhibition. This will fill a major gap in knowledge regarding the use of MNK1/2 inhibitors for the treatment of metastatic disease.

Please briefly describe the effect, if any, of being a Stand Up to Cancer grant recipient may have had on your career. For example, additional funding or tenure prospects, researchers interested in collaboration/working in your laboratory, etc.

This opportunity has positioned me to not only work shoulder-to-shoulder with world leaders in breast cancer and mRNA translation research but has also helped support my career development. I very much appreciated being invited to attend the Stand Up to Cancer Scientific Summit (January 2020), where I could network with other rising Early Career Investigators. At that meeting, I won an award which allowed me to present our work using imaging mass cytometry (IMC), to examine in which cell types of the TME MNK1/2 are most active. The feedback I received at this meeting was unparalleled and helped shape the focus of my recent grant applications.

Has the SU2C Dream Team Grant allowed you to pursue research that would not have been otherwise possible? If so, how?

It is a dream for my team and I to see therapies developed against the kinases that we have been studying in the lab being used to treat women with breast cancer. Without our involvement in this SU2C Dream Team grant, we would not be able to access precious tumor biopsies in order to better understand the impact of MNK1/2 inhibitors on the tumor and on tumor associated cells.

For over a decade, SU2C’s Dream Team grants have developed new and improved approaches to cancer treatment and cure. What is your vision for the next 10 years of metastatic breast cancer research? How do you hope this Dream Team’s research can transform patient’s lives in the decades to come?

MNK1/2 inhibitors are a novel class of therapy that seeks to repair the effects of faulty mRNA translation. Our hope is that we will be able to discover biomarkers of response and resistance to MNK1/2 inhibitors. In doing so, we expect that the clinical observations we make in patients will germinate additional hypotheses testable in the labs of our SU2C Dream Team, and in turn, foster future clinical trials. We predict, based on our recent work and the work of our collaborators, that MNK1/2 inhibitors will be most efficacious when combined with immune-targeted therapies.