The appointments reflect the increasingly integrated nature of modern oncology research, in which laboratory discoveries, clinical trial design, pharmacy operations, patient safety, data management, and professional development must function as a single system. NRG Oncology is part of the National Cancer Institute’s National Clinical Trials Network and coordinates multicenter studies across more than 1,300 research sites worldwide, with a major focus on breast, gynecologic, prostate, and other localized or locally advanced cancers.

Rebecca Arend, MD, MPH, has been appointed Gynecology Oncologist Vice Chair of the NRG Translational Science Committee. A gynecologic oncologist, surgeon-scientist, and clinical trial leader, Arend studies how molecular features of cancer can be converted into more precise methods of screening, prognosis, and treatment selection. Her work includes DNA, RNA, protein, and circulating tumor DNA, or ctDNA, a form of genetic material released by tumors into the bloodstream that can provide a minimally invasive view of cancer biology.

Arend’s research is especially focused on ovarian, endometrial, cervical, and other gynecologic cancers, diseases in which tumors can vary substantially at the molecular level even when they arise in the same organ. Biomarker-driven treatment aims to identify those differences and match patients with therapies most likely to work. As Associate Director of Clinical Research at the O’Neal Comprehensive Cancer Center, Arend oversees trial infrastructure, protocol development, workforce training, and the integration of translational research into clinical programs. Within NRG, she is Translational Science Chair of the Ovarian Subcommittee under the Gynecologic Cancer Committee and is involved in developing early-career oncology investigators.

Robin Lockhorst, PharmD, BCOP, BCPS, has been appointed Chair of the NRG Pharmacy Subcommittee. With more than 15 years of experience at Avera Cancer Institute, Lockhorst has worked across oncology pharmacy, bone marrow transplantation, solid organ transplantation, hepatology, and clinical research. She currently serves as Director of Clinical Research, Oncology, where she is expanding satellite research programs and helping build early-phase trial capabilities across the Great Plains region.

Pharmacy leadership is central to the safe delivery of experimental cancer treatments. Clinical pharmacists review protocols, manage investigational drug services, verify dosing and drug interactions, and help ensure that treatment is administered according to highly specific study requirements. Lockhorst has led operational improvements in these areas while supporting protocol review and multidisciplinary education. Her work has also included mentoring pharmacy trainees and helping advance South Dakota’s drug donation and repository pilot program, an initiative designed to improve access to eligible medications.

David Miyamoto, MD, PhD, has been appointed Radiation Oncology Vice Chair of the NRG Translational Science Committee. A radiation oncologist and physician-scientist at Massachusetts General Hospital, an Associate Professor at Harvard Medical School, and an Associate Member of the Broad Institute of MIT and Harvard, Miyamoto investigates how molecular testing and advanced imaging can make cancer treatment more predictive. His laboratory research has emphasized liquid biopsies, tumor genomic analysis, and imaging technologies for prostate and bladder cancers.

The goal of this work is to identify biological signals that reveal whether a tumor is responding to treatment, developing resistance, or progressing before those changes become obvious through conventional clinical assessments. Miyamoto has led NIH-funded research involving liquid biopsy and prostate-specific membrane antigen, or PSMA, positron emission tomography imaging in patients receiving Lu-PSMA-617 radioligand therapy. This treatment delivers radiation to cancer cells that express PSMA, and biomarkers may help determine which patients are most likely to benefit. Miyamoto has also served in translational leadership roles on major multicenter studies, including NRG-GU015, ECOG-ACRIN-NRG 8185, and the PARTIQoL trial.

Elena Nelson, MBA, CCRC, has been appointed Vice Chair of the Clinical Research Associate Subcommittee within the NRG Protocol Support Committee. Nelson brings more than 15 years of oncology research experience from the University of Florida Health Cancer Center, where she serves as Data Management and Academic Research Consortium Network Manager. In that role, she leads data operations for approximately 150 trials involving solid tumors, hematologic malignancies, pediatric cancers, and early-phase therapies.

High-quality data are essential to determining whether a treatment is safe and effective. Nelson has developed standardized workflows to improve the accuracy, completeness, and timeliness of trial information, including data submitted for NCI-sponsored and experimental therapeutics studies. She is also a RECIST subject matter expert. RECIST, or Response Evaluation Criteria in Solid Tumors, is a standardized system used to measure whether tumors have shrunk, remained stable, or grown during treatment. Nelson has worked with NRG on the RECIST CLASS project and has served as both a member and mentor within the Protocol Support Committee.

Cortney Montgomery, MD, MHSc, has been appointed Vice Chair of the NRG Protocol Support Committee Mentorship Subcommittee. With more than 25 years of experience in oncology research nursing and clinical trial coordination, Montgomery has worked in academic medical centers, comprehensive cancer centers, and direct patient-care settings. At UPMC Hillman Cancer Center, she serves as a Clinical Research Coordinator and Treatment Nurse, managing patient screening, informed consent, investigational drug administration, chemotherapy delivery, and protocol compliance while helping establish a new Clinical Translational Research Center.

Montgomery has coordinated Phase I through Phase IV studies, including industry-sponsored, cooperative group, and investigator-initiated trials. Her clinical research experience spans breast cancer, gynecologic oncology, and early-phase therapeutics, where careful monitoring is particularly important because experimental treatments may involve uncertain dosing, novel mechanisms, or previously unrecognized toxicities. She has also contributed to clinical trial awareness and outreach through the Carol Glock Foundation and has served NRG as a committee member, mentor, and liaison to the Breast Cancer Committee and Uterine Corpus Cancer Subcommittee.

Together, the appointments highlight how cancer research increasingly depends on collaboration across disciplines rather than on isolated discoveries. Biomarker scientists need reliable clinical samples and high-quality datasets; radiation and medical oncologists require pharmacy systems capable of delivering complex therapies; and clinical research teams need experienced mentors to sustain the workforce behind multicenter trials. NRG Oncology said the new leaders will help advance its research while continuing the contributions of outgoing vice chairs. Current committee leadership and member openings are listed on the organization’s website.

Subject of Research: Leadership changes in a major oncology clinical trials network, with emphasis on translational cancer research, biomarkers, pharmacy operations, clinical trial data management, and research mentorship.

Article Title: NRG Oncology Appoints New Leaders to Advance Precision Cancer Research and Clinical Trials

Web References: https://www.nrgoncology.org/Current-Openings ; https://www.nrgoncology.org

References: NRG Oncology leadership announcement and organizational information provided in the source material.

Keywords: NRG Oncology, cancer research, clinical trials, translational science, biomarkers, circulating tumor DNA, liquid biopsy, radiation oncology, gynecologic oncology, pharmacy research, RECIST, precision medicine, oncology leadership, clinical research mentorship

RAS mutations, particularly in KRAS, have long been recognized as pivotal contributors to the pathogenesis and progression of colorectal cancer. However, effective therapeutic strategies to counteract RAS-driven oncogenic signaling have remained limited, largely due to the intricate network of feedback mechanisms that sustain tumor growth. The study zeroes in on the RAS/MEK pathway, which forms a critical axis in tumor cell proliferation, survival, and resistance. Prior preclinical models suggested that MET signaling and its downstream STAT3 activation may serve as alternative survival pathways that cancer cells exploit to bypass MEK inhibition, prompting the rationale for a combined MEK and MET blockade.

The MErCuRIC study utilized binimetinib, a potent small-molecule inhibitor of MEK1/2, in conjunction with crizotinib, a well-characterized MET inhibitor approved for other malignancies. The trial began with a dose escalation phase involving patients with advanced solid tumors to establish the maximum tolerated dose (MTD) and examine safety profiles. This was followed by a dose expansion phase focused specifically on patients harboring RAS mutant metastatic colorectal cancer, aiming to scrutinize therapeutic efficacy and biological response markers.

Twenty patients participated in the dose escalation cohorts, where dosing regimens were meticulously adjusted through a rolling-6 design to optimize tolerability. The investigators determined the MTD to be binimetinib at 30 mg twice daily on days 1 through 21 every 28 days, combined with continuous daily dosing of crizotinib at 250 mg. Notably, dose-limiting toxicities prominently featured hepatotoxicity, as evidenced by grade 3 or higher transaminitis, along with elevations in creatinine phosphokinase and fatigue. These toxicities highlighted the systemic impact and narrow therapeutic window of this pharmacological combination.

Following the identification of the MTD, the trial expanded to include 36 patients diagnosed with RAS mutant metastatic colorectal cancer. Detailed pharmacokinetic and pharmacodynamic analyses performed on blood samples revealed compelling evidence of target pathway engagement, affirming that both binimetinib and crizotinib effectively reached their intended molecular targets in vivo. Complementary analyses of skin and tumor biopsies using c-MET immunohistochemistry and in situ hybridization techniques allowed researchers to interrogate the expression patterns and amplification status of MET, a critical determinant of treatment response.

However, despite optimal dosing and proven target inhibition, the clinical outcomes painted a sobering picture. The most common treatment-related adverse events (TR-AEs) reported were rash, fatigue, and diarrhea, converging with the toxicities noted in earlier cohorts. Alarmingly, nearly 45% of patients experienced grade 3 or higher adverse events, reflecting considerable tolerability challenges that may limit the clinical utility of this regimen. Objective tumor responses were conspicuously absent, with the best observed result being stable disease in just under a quarter of patients, underscoring the limited anti-tumor efficacy of the combined MEK and MET blockade in this setting.

A particularly intriguing molecular observation was the subgroup of patients exhibiting MET “super-expression,” characterized by high immunohistochemical H-scores exceeding 180 and strong MET in situ hybridization signals. Although this biomarker subset accounted for about 24% of patients, only one individual displayed true MET amplification. Unfortunately, this patient discontinued treatment early due to toxicity, precluding any assessment of potential benefit in this biologically defined group. These findings raise important questions about the predictive value of MET overexpression and amplification in guiding MET inhibitor use within RAS mutant colorectal cancer.

Moreover, circulating tumor DNA (ctDNA) analyses revealed that patients presenting with high baseline RAS mutant allele frequencies faced significantly shorter overall survival compared to those with lower mutant allele burdens. This correlation between molecular tumor load and survival outcomes reinforces the aggressive nature of high-terminal RAS mutation burdens and highlights the necessity of considering tumor heterogeneity and clonality in treatment design and prognostication.

The MErCuRIC study thus offers a rigorous and highly detailed examination of the therapeutic landscape for RAS mutant advanced colorectal cancer, shedding light on the intricacies of pathway interplay, resistance mechanisms, and toxicity management. It underscores the enduring challenge of directly targeting RAS-driven cancers, even when sophisticated combination approaches are employed. Importantly, it calls for a deeper understanding of the biology underpinning resistance, and the identification of novel biomarkers to stratify patients who might benefit from targeted therapeutic strategies.

From a clinical trial design perspective, the findings illustrate the critical importance of comprehensive biomarker-driven patient selection and the integration of translational science to unravel resistance pathways. The high incidence of adverse events associated with binimetinib and crizotinib combination therapy suggests that careful attention must be paid to dosing strategies, supportive care, and perhaps the exploration of alternative scheduling or sequencing to mitigate toxicity without compromising efficacy.

While the results are sobering, the endeavor to disentangle RAS mutant colorectal cancer’s complex signaling networks and develop effective targeted therapies remains an urgent priority. This study serves as a pivotal reference point, guiding future research efforts toward more innovative and nuanced therapeutic interventions. It points to the potential value of combination regimens that can overcome resistance pathways, including MET-mediated escape mechanisms, but also highlights the necessity of balancing efficacy with patient quality of life.

In conclusion, the MErCuRIC trial marks a significant milestone in the ongoing battle against RAS mutant colorectal cancer. It demonstrates the formidable challenges inherent in overcoming biological redundancy and therapeutic resistance, and the critical role of precise molecular characterization in guiding clinical decision-making. As research advances, continued exploration of alternative targets, combination strategies, and personalized medicine approaches will be essential to transform the therapeutic landscape for this challenging and prevalent malignancy.

—

Subject of Research: Therapeutic targeting of RAS mutant advanced colorectal cancer using MEK1/2 and MET inhibitors.

Article Title: A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC).

Article References:

Aroldi, F., Elez, E., André, T. et al. A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC).
BMC Cancer 25, 658 (2025). https://doi.org/10.1186/s12885-025-14068-1

Image Credits: Scienmag.com

DOI: https://doi.org/10.1186/s12885-025-14068-1