Exploring 3D Tumor Models to Find Best Therapeutics for Patients
2021; Wolters Kluwer; Volume: 43; Issue: 3 Linguagem: Inglês
10.1097/01.cot.0000734288.90898.72
ISSN1548-4688
Autores Tópico(s)Radiomics and Machine Learning in Medical Imaging
Resumosurgery: surgerySepideh Gholami, MD, Assistant Professor of Surgery in the Division of Surgical Oncology at UC Davis Medical Center, combines a robust clinical practice specializing in surgeries of the gastrointestinal tract, liver, biliary tree, and the pancreas, along with a research focus that includes translational science and clinical trials to advance the understanding of hepatobiliary genetics, microenvironment, and immune profiling. “The goal of my research is to look at the tumor microenvironment of colorectal liver metastases,” Gholami told Oncology Times. “Specifically I'm looking into strategies to augment and find new immunotherapeutic agents for this particular type of tumor. That's it in a nutshell. “I'm interested in colon cancers that have metastasized to the liver, the most common organ for this type of spread. These are the most common metastatic tumors I resect in my clinical practice, so I'm interested in discovering how these tumors can be treated with new immunotherapeutic strategies.” To achieve that goal, Gholami is working beside her mentor Steven George, MD, PhD, Professor and Chair of Biomedical Engineering at UC Davis, and taking full advantage of George's 3D microfluidic device. After tumor samples are resected, Gholami then tries to grow 3D tumors and implant them on the device. When successful, this allows the surgeon scientist to study the immune components and mechanism of therapeutic resistance in these tumors derived directly from the patient.Sepideh Gholami, MD: Sepideh Gholami, MDGholami further detailed, “We really try to recreate the patient tumors in the external world so that we can manipulate and treat them, and figure out how to come up with better treatment strategies.” In other words, instead of just looking at tumor cells under a microscope, Gholami examines an actual tumor with the immune component from the matched patient samples. Three-Dimensional Approach “There are several laboratories focusing on 3D tumor modeling, but we are one of the few labs recapitulating the immune microenvironment ex vivo of these specific liver metastases,” Gholami explained. “We are still early on in our data collection on these specific colorectal liver metastases, but we have confidence that the validated model will allow us to test different therapies on a specific tumor. So instead of giving a drug to a patient and hoping it will work, we can technically take a piece of the tumor and see what the response will be ahead of time. Much of the trial and error in finding the best therapy could be removed.” Asked to describe how the immune components are introduced, Gholami noted, “We draw the patient's blood, so all of the immune cells that are in the patient's blood are introduced into the device after the tumors are implanted. Then we look at how these cells behave on the device. “So far, we've had great success in implanting and getting the tumors to grow, and introducing immune cells into the device. We are now at the next stage where we're trying to manipulate the system and immune conditions with drugs to see what happens. So that's the new, exciting part of it. Our data is still in its preliminary stages and not published yet.” Asked how long it might take to develop a personalized therapy once blood is drawn from a patient, Gholami said, “That's a really good question. The tumors grow within 1-2 weeks. So the hope is that within a very short amount of time we should be able to build the 3D tumor model of a patient and then test the treatments.” As this innovative work continues, Gholami says she's aiming for important overarching goals. “Our aim is to use this device as a personalized medicine tool in order to test patient tumors before patients ever get a treatment, such as prior to a clinical trial. And another goal is to manipulate the system and figure out what would be the best treatment option. We can, for example, activate the immune cells to study mechanism of response/resistance to treatment of specific tumors. And once we understand that, I think then we can hopefully develop new treatment strategies.” Looking Back, a World Away Having earned an undergraduate degree at UC Davis prior to completing medical school and a surgery residency at Stanford University and fellowship in surgical oncology and hepatobiliary surgery at Memorial Sloan Kettering Cancer Center, Gholami said she's come “full circle” by returning to UC Davis. But that's only true pertaining to her higher education. The full circle, in terms of her life, would start and end in her native country of Iran. When she was in high school, she moved with her family to Hamburg, Germany. She later came to the U.S. at the age of 17 in the middle of her senior year. However, it was in Germany that her mother discovered she had breast cancer. It was a reality that would influence Gholami's career path. “I truly think I found my direction by being inspired by my mom's illness,” she reflected, noting that her mother survived and is healthy. “Breast cancer runs in my family, so that really sparked my interest in oncology. My mother was diagnosed right when we moved to Germany. So it was a really difficult transition; it left a mark on me and changed my perspective in terms of what I wanted to do.” As she matured and pursued medical studies, Gholami became more aware of immunology and biology, and gained a sense of the strength of medical intervention. “Initially, I honestly wasn't even aware of surgery as a field. My goal was to go into medical oncology and try to find new therapeutics. I was introduced to surgery in my first medical rotation. I really just wanted to get it out of the way; I had no idea that I would fall in love with it. I found the pace matched my personality, and I liked to be hands-on. Surgery is technical and yet it has some art in it, and obviously it is also mentally challenging. It really has it all.” With her parents and brother still in Germany, Gholami loves to travel back to Europe in non-pandemic times. “I really miss traveling internationally, especially to Europe and Asia,” she lamented. “This year, however, I explored the beautiful California coast and Big Sur, and got to Lake Tahoe.” Pinpointing other activities that occur outside of the laboratory and/or clinical realm, Gholami said she loves to cook, and “I'm pretty addicted to fitness and strength training. And while I do it because I have fitness goals, it also keeps me sane. It's an amazing outlet. Fitness training helps me physically and mentally, which is so essential to my work.” Finally, Gholami has another little-known activity that she revealed with some glee. “I love music and I actually was in a gospel choir for 4 years. That would be very surprising to a lot of my colleagues,” she laughed. Work That Lies Ahead In addition to the work already discussed, and in perfect complement to it, Gholami is involved in creating a new platform trial for immune-augmenting therapies for colorectal liver metastases through SWOG, an NCI-supported organization that conducts clinical trials in adult cancers. “We're just in the beginning phases, designing the trial and going through all the different committees. The objective of the platform is to help develop new immunotherapeutic strategies for colorectal liver metastases.” As this important research work grinds on, Gholami continues to be an active clinician, in equal parts because she loves the clinical work and believes it is necessary to her capability as a researcher. “I really feel like you have to do both,” she said of splitting time between clinic and laboratory. “It's very difficult to come up with good scientific questions when you don't see the challenges and failures in clinical practice. One of the strengths of being a surgeon is that you see patients that continue to present questions, and then you translate that from bedside to bench, and vice versa. I think it's certainly an advantage to be able do both; it helps to know the relevant clinical questions to study in the lab. My long-term goal is to become an independent surgeon scientist, get extramural funding, and continue developing into an excellent clinician focused on translational science and clinical trials.” Valerie Neff Newitt is a contributing writer. Spotlight on Young Investigators
Referência(s)