Q&A: Dr. Niki Zacharias Millward, 2025 KCA Grant Winner
Dr. Niki Zacharias Millward received a 2025 KCA Trailblazer Award for research on “Interrogating the Role of TRIP13 in Sarcomatoid Chromophobe Renal Cell Carcinoma”. Dr. Millward previously received a KCA Research Award in 2023. Dr. Millward is an assistant professor in the Department of Urology – Research, Division of Surgery at MD Anderson Cancer Center in Houston, Texas. We spoke with Dr. Millward about her research and the impact it can have on people with kidney cancer.
Briefly describe your project.
Although chromophobe renal cell carcinoma (chRCC) generally has a more indolent course than other kidney cancers, once it metastasizes it is much less likely to respond to immune checkpoint therapies commonly used for other cancers and to the targeted agents developed for clear cell renal cell carcinoma. Approximately 5% to 10% of patients with chRCC will develop aggressive metastatic disease, and developing effective systemic therapies for this patient subset represents a tremendous unmet need. Approximately 58% of metastatic chRCC cases have TP53 gene mutations. TP53 is a critical tumor suppressor gene and plays a central role in maintaining the genomic stability of the cell. We found thyroid hormone receptor interacting protein 13 (TRIP13) to be upregulated in preclinical models of chRCC and in tissue samples from 76 patients with chRCC and TP53 mutations. In this grant, we will interrogate the role of TRIP13 expression in metastatic chRCC biology.
What do we know about chRCC now that we didn’t a few years ago?
Several recent manuscripts have shed light on the biology of metastatic chRCC. We now know that metastatic chRCC has hypersensitivity to a cell death mechanism called ferroptosis (Zhang L, et al. PNAS, 2022; 119(28): e2122840119). In addition, we know that indolent chRCC is characterized by chromosomal loss while aggressive chRCC regions (Kapur, P, et al. JCI Insight, 2024; 9:10: e176743) and metastatic chRCC tissues (Casuscelli, J, et al. JCI Insight, 2017, 2(12):e92699) have chromosomal copy number gains. In addition, chRCC has an “immune-cold” profile, meaning it has few T-cells within the tumor tissue (Labaki, C, et al. JCO, 2025; 43(23): 2639). In the clinic, the recent publication out of MD Anderson (Moussa, MJ, et al. JITC, 2025, 13:e010958) found better response to nivolumab plus ipilimumab in patients with sarcomatoid chRCC. All of this data implies that there are significant differences in the biology of aggressive chRCC, which usually has sarcomatoid morphological features, than indolent chRCC.
How does this current project build on your prior grant-winning research?
Our work builds on our previous KCA funded work. Specifically, it builds from the ongoing KCA collaboration with Tempus via the KCA Postdoctoral Fellow, Nathan Maulding. Using targeted DNA profiling (Tempus | xT), whole transcriptome gene expression (Tempus | xR) and clinical data from 168 de-identified chRCC samples, we found TP53 mutations in 76 of 168 chRCC patient samples (45%) and that the samples with TP53 mutations had higher expression of TRIP13 than TP53 wildtype tumors (p < 1 x 10-10). In a related KCA funded project led by urological oncology fellow Dr. Elizabeth Ellis, TRIP13 expression was identified in sarcomatoid chRCC cell line UOK276 and in sarcomatoid chRCC patient-derived xenograft animal model.
What kind of next step or follow-on research questions do you think might come from your eventual findings?
The main goal of our project is to determine if TRIP13 is a therapeutic vulnerability and if TRIP13 expression can be used as a prognostic marker in metastatic chRCC. Follow-up questions would be to further the development of a TRIP13 inhibitor such as DCZ0415 and to validate TRIP13 expression in additional patient cohorts.
What about your research could be most exciting for patients and families?
This is an exciting time in kidney cancer research. With the advent of advanced bioinformatic tools and platforms, we are now able to dissect the molecular distinctions between indolent and metastatic disease—even within rare kidney cancer subtypes. These insights can be validated using robust preclinical models, enabling researchers to test hypotheses and refine therapeutic strategies before advancing them to clinical trials.
What motivates you?
As a PhD scientist, my work is entirely focused on research—and I truly love what I do. Each day brings something new: designing new projects and experiments, analyzing data, collaborating with colleagues, and working with trainees. At MD Anderson, I have the privilege of working alongside exceptional physicians like Drs. Nizar Tannir, Pavlos Msaouel, Jose Karam, Brittney Cotta, and Surena Matin. Their clinical expertise and collaborative spirit have been invaluable in deepening my understanding of the progression and treatment landscape of chRCC. Our team shares a deep passion for this work, driven by the potential to make a meaningful impact on the lives of patients with kidney cancer.
Has KCA’s funding furthered your research and/or other funding opportunities in any specific ways?
One of the most impactful ways the KCA has influenced my research is by fostering a collaborative community for renal cell carcinoma investigators. Through platforms such as hands-on KCA workshops and the International Kidney Cancer Symposium (IKCS), I’ve had the opportunity to engage with fellow researchers, share ideas, and explore new scientific directions. The KCA has also connected me with patient advocates, offering invaluable insight into the real-world challenges faced by those living with kidney cancer. Many of my external collaborations were initiated through these KCA-supported interactions, making it a vital resource for both scientific advancement and patient-centered research.