Trailblazers

Hania A. Al-Hallaq

WM: In lay terms, what is medical physics, and how does physics contribute to the practice of medicine?

HA-H: We study the principles of physics and apply them to medical treatments that involve the use of radiation. We work in conjunction with the radiation oncology physicians. Physicians determine if a patient needs radiation, how much and to which areas of the body. The medical physicist works on ensuring that the calculations are accurate and that treatment machines are working correctly so that the physician’s treatment plan is delivered to the patient as intended. Medical physicists are also heavily involved in innovating cancer treatment—by designing new treatment machines and software tools or implementing new technologies into the clinic in a safe manner. We spend a lot of time analyzing data and proposing solutions to improve the safety and quality of treatments. At academic centers like Emory, we also train the next generation of medical physicists.

WM: How do patients benefit from X-ray and 3D surface imaging modalities for breast cancer treatments?

HA-H: A radiation plan is developed based on a CT scan of the patient in the treatment position. When the patient returns for treatment (usually for many sessions), it’s important to ensure that the patient is positioned in the same way as when the radiation plan was developed. It’s amazing that radiation treatments have been tailored to individual patients for so long, but the challenge lies in reproducing this plan that is uniquely tailored to the patient’s anatomy. Because we have X-ray capabilities built into our treatment machines, we use X-ray imaging to re-position patients for treatment to match the planned position. Surface imaging is a unique method of using light instead of ionizing radiation to map a 3D model of the patient’s body surface. It can also track that surface in real time to allow us to observe changes due to breathing or a deep breath-hold. It turns out that during a deep breath-hold, the tissue targeted by the physician during breast cancer irradiation naturally moves away from critical organs like the heart and lungs. This is a wonderful advantage allowing physicians to treat breast cancer while reducing some of the side effects. But because treatments are tailored to the patient’s anatomy, we need to make sure that patients can reproduce their breath-hold in addition to their planned treatment position. Surface imaging allows us to accomplish this without the need for ionizing radiation, reducing the patient’s exposure to harmful radiation. And because we can keep the surface imaging cameras on indefinitely, we’ve also been able to make improvements in the quality of treatment since we physicists are constantly analyzing the data and learning from it.

WM: What are you most excited about in your research?

HA-H: There are many artificial intelligence (AI) tools being developed to make the radiation treatment workflow more efficient and robust. But implementing these tools into clinical use is challenging because sometimes they make things less efficient, or they create new error modes. I’m excited about learning how humans will interact with these tools and identifying ways to make the tools more useful in our field. In a sense, learning about how humans use AI will help us learn about the qualities, both good and bad, that make us human.

DANIEL M. HALPERIN

WM: You joined Winship in September 2024. What made you decide to come to Winship from MD Anderson?

DH: There are so many wonderful things about Winship, and it is difficult to name just one. However, the opportunity to contribute to the ongoing growth and development of an organization of such amazing people was impossible to pass up. In my own area of neuroendocrine tumors (NETs), there is a clear need for clinical care and research in this region, and there is a strong commitment from our leadership to develop into a destination center of excellence for patients with NETs. But more broadly, this is such an exciting time in the organization. We are growing and learning on a daily basis, and it is so invigorating to be a part of that process.

WM: What are you most excited about in your research right now?

DH: We are involved in several studies of agents at different points in their development cycle, and each is exciting in its own way. At the more advanced end of the spectrum, we have ongoing and oncoming clinical trials of more advanced radioligand therapies targeting the somatostatin receptor. The currently available agent has been a tremendous advancement for our patients, but there is substantial opportunity to improve the outcomes for those patients. We are also very excited to be involved in the early studies of a new cellular therapy for patients with NETs, which is an entirely new approach for our patients. It takes advantage of a new target, making it a potential option for patients who would not benefit from our current radioligands. Those patients are in particularly profound need of new options, so we are very excited to have something to offer.

WM: How will this research benefit patients with neuroendocrine tumors (NETs)?

DH: While we must always bear in mind that experimental therapies are by definition not yet known to provide benefit, offering and systematically evaluating new and innovative therapies will lead to more options in the future to further improve the lives of our patients. We are hopeful about the potential of the specific experimental agents that we are bringing into the clinic at Winship to reduce the burden of suffering for our patients, both here in Georgia and globally. However, regardless of the outcome of each specific trial, each completed study successfully moves us toward better lives for our patients. And our patients inspire us every day to keep working toward that reality.

Beryl Manning-Geist

WM: What are you most excited about in the area of gynecologic oncology right now?

BM-G: Honestly, it is such an exciting time for the field. First, the rapid advancements in targeted therapies and immunotherapies are revolutionizing how we treat gynecologic cancers. We're moving beyond traditional chemotherapy, offering patients more personalized and potentially less toxic options. It is incredibly rewarding to see firsthand how these innovative treatments can improve outcomes and quality of life for patients with ovarian, endometrial and cervical cancer. Last week alone, we opened two clinical trials that will bring these targeted treatments to bedside for women with recurrent endometrial and ovarian cancer. We will soon be opening another clinical trial at Emory that I designed while at Memorial Sloan Kettering Cancer Center that replaces chemotherapy with targeted therapy at time of diagnosis in women with low-grade serous ovarian cancer, a less common, but aggressive, type of ovarian cancer that grows more slowly than high-grade ovarian cancer.

Beyond advances in targeted and immunotherapies for treatment, improved understanding of cancer genomics is opening up new avenues for early detection and prevention so that we can intercept cancer in its earliest stages to save lives. Our division recently opened a clinic for patients with inherited risks of gynecologic cancers, and we have started a large-scale biobanking project with the intention of designing an early detection test for ovarian cancer.

And finally, as a surgeon, I'm devoted to the continuous refinement of minimally invasive surgical techniques, including robotic surgery. These technological advancements allow us to perform complex procedures with greater precision, smaller incisions and faster recovery times for our patients.

WM: How has gynecologic oncology changed/improved?

BM-G: Gynecologic oncology has undergone a remarkable transformation in recent years. Perhaps the most significant change is the shift toward a more multidisciplinary and personalized approach to patient care. We now work much more closely with radiation oncologists, pathologists, geneticists and other specialists here at Emory who are truly leaders in the field. Every patient with gynecologic cancer who walks through our doors receives an individualized treatment plan designed by this multidisciplinary team that is tailored to their needs and cancer characteristics. This collaborative approach has significantly improved outcomes.

WM: Why is this important for women?

BM-G: These advancements are profoundly important for women for several reasons. First and foremost, they offer hope. Hope for longer survival, improved quality of life and even the possibility of cure for cancers that were once considered almost universally fatal. The development of less invasive surgical techniques means women can recover faster and return to their normal lives sooner. The focus on personalized medicine means that treatments are becoming more effective and less toxic, that we are minimizing side effects and improving overall well-being. But beyond the individual benefits, these advancements are important for all women because they represent a broader shift towards prioritizing women's health. Investing in gynecologic oncology research and care sends a powerful message that women's health matters. It's about empowering women to take control of their health, knowing that they have access to the most cutting-edge treatments and the best possible care. Ultimately, we hope that continuing to move the needle on gynecologic cancer care gives women more time with their loved ones, allowing them to live full and healthy lives.

Wei Zhou

WM: What have you learned about the tumor suppressor gene SOX7 and its role in cancer?

WZ: The Sox7 story centers around the WNT signaling pathway, a network of proteins that transmit signals into cells, which is always activated in colon cancer through genetic changes in the APC or beta-catenin genes. When we began our work on prostate cancer, it was known that WNT signaling is activated, but genetic changes in these two genes were not found. We discovered the missing piece, Sox7, which physically interacts with beta-catenin to normally suppress its function. In most colon cancers and half of prostate cancers, the expression of Sox7 is suppressed. Because there is no Sox7, beta-catenin is overactivated, driving cancer development. Other laboratories have followed up on our work and demonstrated that Sox7’s function is suppressed in lung, breast, kidney and ovarian cancers. More recently, we discovered that another marker for prostate cancer, PSMA, is regulated by Sox7. Active Sox7 keeps PSMA levels low, but when Sox7 is silenced, PSMA levels surge, contributing to cancer progression. Our work suggests that restoring Sox7 function could offer a promising therapeutic approach for human cancers.

WM: What does it mean to study "mechanisms," and how can they lead to new and better targeted cancer therapies?

WZ: Mechanisms are the details of how things work. For example, when discussing the mechanism of cell growth, you can envision it as controlling the speed of a car. The accelerator is the oncogene, and the brake is the tumor suppressor. They interact with many other car components to control the speed of that car. If any one of these components fails, you lose speed control, and uncontrolled cell growth is a hallmark of human cancer. We study mechanisms to figure out how everything works together, and more importantly, what went wrong in cancer. These understandings are essential for developing better cancer therapies. For example, if a type of cancer relies heavily on a particular abnormal onco-protein for survival, that protein becomes a potential Achilles’ heel, and we can develop drugs to inhibit its function. Different cancers, even within the same organ, can have different mechanisms. By understanding the specific mechanisms driving a cancer subtype, we can evaluate the most effective treatment, which is the idea behind personalized therapy.

WM: What are you most excited about in your research?

WZ: Currently, we are most interested in sex differences in cancer development. It turns out that for most cancers, the incidence is higher in males than in females. There are many reasons for this difference, but we recently discovered that in smoking-related cancers with the loss of the LKB1 tumor suppressor gene, there is a two-fold difference in incidence based on sex. In this specific case, the innate immune system in females is responsible for the suppression of this cancer subtype. The innate immune system is the body's first line of defense against pathogens or cancer because it can detect these entities without prior exposure. We are currently studying this immune-based mechanism in detail so that we can develop a new treatment strategy for this cancer subtype.