The Pursuit of a Cancer-Free Future

The prospect of achieving remission after a difficult chemotherapy or surgical journey often brings cancer patients immense relief and hope to reclaim their health. However, for individuals diagnosed with cancer types that are prone to relapse after treatment, this sense of hope and relief is often all too short-lived. Working to change this is board-certified medical oncologist William Matsui, MD, who treats cancers affecting the blood, bone marrow, and lymph nodes through the Hematologic Malignancies specialty within UT Health Austin’s Livestrong Cancer Institutes.

Dr. Matsui is a professor in the Dell Medical School Department of Oncology and a courtesy professor in the Dell Medical School Department of Internal Medicine. He also serves as the Deputy Director and the Director of Hematological Malignancies Program for the Dell Medial School Livestrong Cancer Institutes.

Learn how Dr. Matsui brought blood cancer care within reach for Central Texans.

<br>Dr. Matsui’s research is inspired by his observations treating patients with conditions such as multiple myeloma, a cancer that affects a form of white blood cells called plasma cells that help the body fight infection.

Targeting Cells Linked to Cancer Relapse

For almost three decades, Dr. Matsui has sought to identify cell types that enable relapse in multiple myeloma, pancreatic cancer, and leukemia, a cancer that affects the blood and bone marrow.

“Within a tumor, there are millions of cells performing a variety of functions. Some of these cells, which we call cancer stem cells, drive tumor regrowth if they are left behind after surgery or chemotherapy,” explains Dr. Matsui. “Having identified these cells in the three forms of cancer we study, our laboratory now hopes to better understand how these cells function so that they can be targeted during treatment.”

Last fall, Dr. Matsui and his team began developing an antibody treatment for pancreatic cancer stem cells in an effort funded by Texas Biologics, a joint initiative between the Cockrell School of Engineering and College of Natural Sciences at The University of Texas at Austin. The project is in collaboration with Jennifer Maynard, PhD, a professor in the Cockrell School of Engineering McKetta Department of Chemical Engineering, who will synthesize the antibodies.

Accommodating Cellular Diversity

“One challenge our team faces in targeting cancer stem cells is that the cell types that act as cancer stem cells can vary by person, cancer type, or even cancer stage,” says Dr. Matsui. “For example, the cell types associated with relapse during the early phases of leukemia may be different from those that should be targeted after many rounds of treatment.”

Although the variability in cancer stem cells complicates the team’s research, it also enables them to discover individual factors that influence a patient’s response to cancer treatment. Currently, Black men develop multiple myeloma at higher rates than the general population. Dr. Matsui’s laboratory is investigating one potential culprit for this disparity, the BCL7A gene that tends to be mutated in Black multiple myeloma patients.

Across the general population, BCL7A mutations are linked to lymphoma and myeloma, cancers associated with two types of white blood cells involved in the body’s immune response. The plasma cells involved in myeloma are more mature forms of the B cells affected by lymphoma.

“Black patients with multiple myeloma have higher rates of BCL7A mutation, but those with lymphoma do not,” shares Dr. Matsui. “Our team wants to establish whether this mutation leads to plasma cell diseases rather than B cell diseases in these patients.”

Learn how healthy immune cells work together to protect your body from infection.

<br>Black multiple myeloma patients tend to have lower rates of mutations in the TP53 gene. Mutations in TP53 are associated with all forms of cancer because the gene codes for a protein known as p53 that acts as a tumor suppressor by regulating cell division and cell death. Without a proper copy of TP53, cells may not make enough p53 protein to prevent tumor growth.

“TP53 mutations are thought to play different roles in different forms of cancer,” explains Dr. Matsui. “In the context of multiple myeloma, people with this mutation tend to go into remission at the same rate as those without the mutation, but they are more likely to relapse sooner.”

In April, the team published an article in Blood Advances, a peer-reviewed scientific journal that focuses on research related to hematology and is an official publication of the American Society of Hematology (ASH). Their research demonstrated that multiple myeloma cell samples altered to remove the TP53 gene were more resistant to anti-tumor drugs and were more likely to display tumor-initiating properties in line with cancer stem cells. The mutation was associated with high activity in the Notch signaling pathway that helps govern development.

“Our research showed that Notch pathway signaling induces tumor-initiating properties in myeloma samples without the TP53 gene, but not in regular myeloma samples,” shares Dr. Matsui. “It’s possible that multiple myeloma patients with a TP53 mutation could benefit from an extra therapy that targets the Notch pathway.”

Connecting the Laboratory and the Clinic

Dr. Matsui plans to follow this publication with research involving gamma secretase, the enzyme that activates the Notch pathway. He believes that gamma secretase could play a role in conditions other than multiple myeloma and recently received a grant from the Leukemia & Lymphoma Society to study Notch signaling and gamma secretase activity in cells sampled from leukemia patients.

“This illustrates how research inspired by a clinical question can shed light on a basic biological principle that is applied in turn to other clinical situations,” says Dr. Matsui. Just as Dr. Matsui’s research interests were informed by experiences treating patients, he brings an investigative rigor to his clinical practice, noting parallels between the diagnostic process and the scientific method by which researchers evaluate a hypothesis.

“When a patient first comes to the clinic, the cause of their illness is not always apparent. Their symptoms could be related to several different conditions, but a doctor cannot treat all these possibilities at once,” explains Dr. Matsui. “Instead, we take what we know about the patient and determine the most likely cause of their illness. Then, we run tests to validate this hypothesis, changing it if needed based on the evidence. Once we have identified a patient’s condition, we can move forward with treatment.”

“Because I devote my time to treating and researching a select set of cancers, I am afforded a unique understanding of these conditions that allows me to better serve my patients,” continues Dr. Matsui. “This expertise makes a difference when caring for patients with these rare and often serious forms of cancer.”

For more information about the Livestrong Cancer Institutes or to schedule an appointment, call 1-833-UT-CARES (1-833-882-2737) or visit here.

To learn more about the Hematologic Malignancies specialty within the Livestrong Cancer Institutes, click here.