Following the science to breast cancer breakthroughs

 

Current Lynn Sage Scholar Dr. Marc Mendillo leans on his own personal experience with breast cancer to inspire his research.

“My godmother and my cousin (during her first pregnancy!) were diagnosed with breast cancer. I suspect we all know somebody who has been stricken with breast cancer. While great strides have been made, there are still far too many people that succumb to this disease.”

Dr. Mendillo’s research group takes an alternative approach to anti-cancer strategies, focusing on the cellular stress response system.

“The vast majority of cancer research groups — both in academic and in big pharmaceutical labs – actively map the mutational ‘drivers’ of cancer. These are the mutations that directly turn a non-cancer cell into a cancer cell. Our lab is pursuing a fundamentally different strategy. We are attempting to exploit the pathways that are generally unimportant in normal cells that become essential in the context of cancer. We refer to this as the ‘non-oncogene addictions’ of cancer cells.

 

“We always follow where the science takes us. We have an exorbitant amount of data to suggest the cellular stress response networks that we study are very relevant in breast cancer. We have directly examined more than 2,000 human tumors and bioinformatically analyzed thousands of others. We find that high levels of activation of these stress networks are associated with the most aggressive breast cancers.

 

“For example, the life of a metastatic breast cancer cell involves growth despite having limited nutrient and oxygen availability. Eventually, these cells leave the initial site of the tumor, invade surrounding tissue, survive passage through the circulatory system, and colonize foreign tissue with a fundamentally different environment. This all happens while being exposed to various cytotoxic chemotherapeutic drugs.  Ironically, the pro-survival cellular stress response network acts to enable tumor cell survival – all to our own detriment. We believe that targeting this ‘addiction’ of cancers to the stress response network offers a powerful and unique type of anti-cancer strategy.”

Unfortunately, it is very difficult for young researchers with new or alternative strategies to secure funding. The Lynn Sage Foundation is committed to innovative research and the brilliant minds diligently working to improve the prevention and treatment of breast cancer.

Dr. Marc Mendillo, Lynn Sage Scholar, gives a tour of his Northwestern lab.

“I can’t emphasize enough how important the funding from The Lynn Sage Foundation is for our lab. It funds our most innovative and most daring work. For example, we’re developing a technology that leverages the dramatic reduction in the cost of DNA sequencing to map gene-drug interactions at an unprecedented throughput. We are using this to address a simple, but important question: Why do some cancers respond to treatments, while others do not?

 

“Using genome engineering allows us to switch on and off any one of the approximately 25,000 genes encoded in our genome. We use DNA sequencing to read DNA barcodes (unique labels that are encoded in the DNA itself) that mark the particular gene we are toggling in individual cells. We grow these distinct cells in complex pools in the presence or absence of different drugs (or other conditions). After treatment, we can isolate and use sequencing to read the DNA barcodes to learn how each gene affected the growth of the cancer cells during exposure to each drug. This allows us to conduct tens of thousands of experiments simultaneously. Our initial application of this technology is to turn on or off different components of the stress response machinery, but we eventually aim to expand this study to include additional genes and mutations found in cancer.”

Managing a laboratory dedicated to one of the world’s largest problems is challenging. Modern technology is thankfully escalating the pace of research by increasing both the number of experiments that can be undertaken and the speed with which they are analyzed. This requires a sophisticated team with diverse skill sets.

“Our work is heavily dependent on bioinformatics. Our experimental approaches generate massive amounts of data. Each one of our experiments can result in 50,000 to 1.5 million data points depending on the experiment. We use this data to generate hypotheses and interrogate the seemingly infinite amount of data that is publicly available.

“I am very fortunate to have a fantastic and dedicated team that I truly enjoy working with. This team includes one PhD student, two MD/PhD students, two postdoctoral fellows, and a PhD-level lab manager. I find it difficult to articulate how satisfying it is to work with brilliant people to address important problems. It is truly wonderful. We are also fortunate to be a part of the Department of Biochemistry and Molecular Genetics. This department is dedicated to state-of-the-art molecular research and comprises brilliant and welcoming scientists and clinicians who are committed to their research, collaboration, and making an impact on the treatment of human diseases.”

Dr. Mendillo’s team extends beyond his lab and the Department of Biochemistry and Molecular Genetics at Northwestern Lurie Cancer Center. His curious and generous spirit led him to a wonderful collaboration of Lynn Sage Scholars.

“Through The Lynn Sage Foundation, I have gotten to know Drs. Dai Horiuchi and Athan Vassilopoulos – fantastic breast cancer biologists located in different departments at Northwestern. We met at a Lynn Sage Foundation event and realized we have common research interests and complementary areas of expertise. Our collaboration is just getting started and I’m excited about where it is going!

“I can’t emphasize enough how grateful we are to The Lynn Sage Foundation, and all its supporters. The level of commitment you have for cancer research and raising funds to support this work is truly inspiring. It leaves me with an immediate and immense human connection and responsibility for the work we are doing. It serves as a reminder of the importance and high expectations the community has for our work.”

Your support funds the ground-breaking discoveries of Dr. Mendillo. Please include the Lynn Sage Scholars in your year-end giving and support their innovative anti-cancer research. We look forward to updating you on their progress.