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  • Tufts Breakthrough

Cancer Research: A Growing And Changing Field

With the development of more sensitive cancer detection methods, cancer diagnoses are becoming more common. As a result, the field of cancer research grows rapidly. Professor Madeleine Oudin, Assistant Professor at the Tufts Department of Biomedical Engineering and the Principal Investigator of the Oudin lab, is dedicated to defining the microenvironmental factors that promote cancer metastasis. Cancer metastasis refers to the migration of cancer cells; it is a major cause of cancer-induced deaths. Thus, research examining the causes of metastasis can generate important implications for cancer treatment.

After earning a B.S. in Biochemistry from McGill University and completing a master’s program in Pharmacology, Professor Oudin pursued her PhD in studying the role of adult brain stem cells in King’s College London. As she continued her research, she noticed that stem cell and cancer cells share the tendency to migrate. This realization led Professor Oudin to dedicate her Post-Doctorate and current research to cancer metastasis.

For a long time, biologists have studied cancer on a cellular scale through identifying oncogenic DNA mutations and tumor-specific cell markers. While studying cancer cells remains crucial to cancer research, some scientists are now viewing cancer from more comprehensive perspectives that entail the immune system and stem cells. The researchers at the Oudin lab are among this growing crowd.

Professor Oudin explained that the Oudin lab primarily studies the contribution of microenvironments to metastasis and drug resistance.

“My lab has focused on trying to understand cancer metastasis——how cells from a primary tumor are able to spread to other areas in the body. This [process] is responsible for 90% of deaths linked to cancer…[We intend to answer the questions] ‘which tumor is going to become metastatic?’ and ‘how we can better tailor treatments for tumors that are already metastatic?’”

“We are [also] trying to understand how different components of the local tumor ecosystem can contribute to the development of tumor drug resistance, so that we can track resistance in a patient and find new drugs to treat these tumors.”

Research in the Oudin lab also supports a currently underrepresented but much needed cancer treatment that target metastatic cancer cells. Chemotherapy——the most common cancer therapy in use——targets primarily highly proliferative cells.

“Metastatic patients will have growing cells and moving cells. If you kill the proliferating cells [but]…leave behind the moving ones, they will…make new tumors. So, we are trying to find complementary approaches [to many existing cancer treatments].”

As a result, the Oudin lab tries to identify metastasis drivers among factors in tumors’ local environments, such as matrix protein gradients, electrical properties, and stiffness properties. By inhibiting the environmental mediators of tumor metastasis and drug resistance, one can not only kills cells that already exhibit these properties, but also prevent more tumor cells from developing them. Furthermore, this approach also circumvents the negative side effects of directly cytotoxic cancer treatments such as chemotherapy.

“[When you] induce cell deaths with chemotherapy, immune cells will come in to eat up the dead cells. Those [immune] cells can also secrete a lot of factors that are prometastatic.”

One example of a microenvironmental factor that directs metastasis, as illustrated in a 2016 Molecular Biology of the Cell article by Professor Oudin and colleagues, is fibronectin gradient. Fibronectin is an important protein component of the extracellular matrix. Tumor cells that express the protein Mena invasive are attracted to high fibronectin concentrations. Additionally, previous studies have reported high fibronectin concentration around blood vessels, which can help metastatic tumor cells circulate throughout the body. In this way, fibronectin serves as a road sign that navigates Mena-invasive-expressing tumor cells to the body’s fastest highway.

As a result, it is important that scientists discover a way to inhibit the permissive effects of fibronectin on tumor migration by blocking tumor-fibronectin interactions. But how they can do this? That is a hard question to answer. Because, given the indispensable role fibronectin plays to support normal cell functions, interference with fibronectin functions would likely have widespread negative side effects on healthy cells.

One clear clinical application of the knowledge on the metastasis-permissive function of fibronectin pertains to drug delivery. According to Professor Oudin, fibronectin receptors, which are commonly present on tumors, can serve as cancer-cell markers that direct drug-containing nanoparticles to cancer cells.

While environmental cues drive cancer cell movement, cancer cells can also, in return, remodel their environments to better prepare themselves for migration. Professor Oudin cited breast cancer cells’ manipulation of collagen as an example.

“Collagen is one of the most abundant proteins in breast tissues. They can have this curly, coil structure, [which] is not very conducive of cell [migration], because it’s [too] loose…But [tumor cells] can reorganize collagens into straight fibers that can provide highways for tumors to migrate on.”

Besides conducting basic research, Professor Oudin, technically an engineering professor at Tufts, also leads projects that focus on developing better tools for cancer scientists.

“[We use] microfluid devices, tissue-engineering approaches to better create environments in vitro, which mimics what’s present in the tumor, so that we can study these processes more accurately…We [also] turn to tissue engineering to recreate organs in vitro, to study why [cancer] cells tend to go to certain organs and not others.”

In addition to talking about her specific research, Professor Oudin also addressed several slight common misconceptions about cancer. Firstly, cancer is one big monolith of diseases that needs only one type of treatment.

“[Cancer] is hundreds of different diseases, depending on what organ your cancer’s in and what type of mutation it has…you really need to treat each cancer individually; there is never going to be a universal cure for cancer.”

In the same vein, Professor Oudin warned against exaggerations of the effects of certain food or habits on cancer in popular science articles. Because the causes of cancer are inherently diverse and complex, there is no such thing as one deterministic factor behind cancer development. And on a perhaps slightly depressing but realistic note: one big reason driver of cancer is simply bad luck.

“Cancer originates from [DNA] mutations. You can inherit mutations from your family, such as the BRCA mutations. Environmental components, such as smoking and UV radiations, can drive mutations. But it turns out that bulk of mutations that drive cancers happen just as results of mistakes in DNA replication, and that you can’t prevent.”

Additionally, Professor Oudin advocated for more care for patients with metastatic cancer.

“There has been a lot of push to prevent cancer and detect it early, which is important. But there are also a lot of people already living with metastatic diseases who want and deserve better treatments. So, we can’t just [focus] on early detection and prevention. We need to also make cancer a disease that you can live with.”

Lastly, Professor Oudin encouraged students interested in pursuing a research career to explore different fields of study and ways of being involved in scientific research.

“It’s OK to change and move around. What’s exciting about science is that you can do your PhD in one thing, and your Postdoc in something else. Also take advantage of [research opportunities] to get exposed to different fields. Remember that there are also many ways to be involved in scientific research that are not in the academia, and not by being a professor. [Those opportunities may lie in industries of] biotech, law, communication about health and science.”

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