Targeting CNS Cancers with Precision Radiotherapeutics
By: Soumya Shashikumar, MBiotech
Interviewee: Marc Hedrick, MD, MBA, President and CEO, Plus Therapeutics
Targeting CNS Cancers with Precision Radiotherapeutics
By: Soumya Shashikumar, MBiotech
Interviewee: Marc Hedrick, MD, MBA, President and CEO, Plus Therapeutics
Central nervous system (CNS) cancers remain among the most complex and difficult-to-treat malignancies. With limited FDA-approved therapies and often poor prognoses, patients with brain and spinal cord tumors face considerable challenges.
Glioblastoma — which accounts for nearly half of all primary malignant brain tumors and affects approximately 3.2 per 100,000 Americans (around 15,000 new cases) annually — is one of the most recognized examples of this unmet need.
Another, often underappreciated, form of CNS involvement occurs in leptomeningeal metastases — secondary tumors that originate outside the CNS but invade the cerebrospinal fluid that surrounds and cushions the brain and spinal cord. These are reported in 5% to 8% of cancer patients, and approximately 132,000 individuals are diagnosed in the US each year.
Radiation remains a foundational treatment approach; however, traditional methods often damage healthy tissue, thereby limiting the dose that can be safely delivered.
In this Xtalks Clinical Edge interview, Dr. Marc Hedrick, President and CEO of Plus Therapeutics, discusses how the company is exploring targeted radiotherapeutics for CNS cancers — with a focus on glioblastoma and leptomeningeal disease — using precision delivery techniques designed to enhance therapeutic selectivity and clinical feasibility.
From Pediatric Surgery to Radiotherapeutic Development
Dr. Hedrick began his career as a pediatric and vascular surgeon at the University of California, Los Angeles (UCLA), where he also led research at the Laboratory of Regenerative Bioengineering and Repair.
During a fellowship at the University of California, San Francisco (UCSF), he worked with a pioneering team developing in utero interventions for fetuses with life-threatening congenital conditions.
“You could diagnose it [devastating life-threatening complications] by ultrasound before, so you knew a disease tsunami was coming for these kids,” he said.
This early exposure to treating high-risk populations informed his transition from academia to biotechnology. Since then, Dr. Hedrick has been involved in developing treatments across pediatric and adult populations, particularly where existing options remain limited.
“We are very reliant on physician leaders who have a heart for these patients. And the company is the quarterback in a way for harnessing all these talents and commercial enterprises, physicians, scientists and governments to be able to deliver this. It’s the ultimate orchestration.”
— Marc Hedrick, President and CEO, Plus Therapeutics
“We are very reliant on physician leaders who have a heart for these patients. And the company is the quarterback in a way for harnessing all these talents and commercial enterprises, physicians, scientists and governments to be able to deliver this. It’s the ultimate orchestration.”
— Marc Hedrick, President and CEO, Plus Therapeutics
Addressing the Therapeutic Gap in CNS Cancers
Plus Therapeutics is focused on CNS malignancies, where therapeutic innovation has lagged. According to Dr. Hedrick, several tumor types within this category have not seen new FDA-approved therapies in over a decade.
Radiation remains a central approach to treating these tumors, but the ability to deliver it precisely is limited by the therapeutic index — the balance between effective tumor dose and damage to surrounding tissue.
“We’re talking about a 100-to-1, so not 1-to-1, not 3-to-1, but a 100-to-1 therapeutic index is possible, meaning for every one molecule of radiation you’re getting to say the bone marrow, you’re getting 100 to the brain cancer or the spinal cord cancer. Those are terrific odds, and we’ve proven that in at least two different kinds of cancer and likely a third here coming relatively soon,” said Dr. Hedrick.
The company’s strategy is to improve the therapeutic index by combining a radiotherapeutic agent with targeted delivery techniques that aim to concentrate radiation at the tumor site while minimizing exposure to critical organs.
Plus Therapeutics is employing two methods specifically designed for the CNS anatomy. For glioblastoma, the team uses convection-enhanced delivery (CED), which infuses therapy directly into brain tissue through implanted catheters. For cancers affecting the cerebrospinal fluid (CSF), like leptomeningeal metastases, an intrathecal port system — reminiscent of chemotherapy ports — allows for repeated, localized access to the fluid space without significant systemic exposure.
Leptomeningeal Cancer: A Rising Complication
One of the main areas of focus for Plus Therapeutics is leptomeningeal metastases, which arise when primary cancer cells spread to the CSF. This complication is being seen more often as patients with primary cancers like breast, lung and melanoma live longer due to improved therapies.
“So, arguably, there’s an epidemic of leptomeningeal metastases in the community because more and more people are living longer with breast cancer or lung cancer, melanoma, but those cells aren’t cured,” he said.
Dr. Hedrick estimated that leptomeningeal cancer likely affects between 250,000 and 400,000 individuals in the US each year, if one takes into account both those who are undiagnosed and diagnosed.
Despite its frequency, leptomeningeal metastases lacks FDA-approved treatments. Patients typically survive four to six weeks without treatment, and up to a few months with intervention. As Dr. Hedrick put it in a sobering observation, “Even though there’s nothing approved, doctors will throw the kitchen sink at many of these patients to try to extend their life.”
Plus Therapeutics is exploring the use of an intrathecal port system, similar to those used for chemotherapy, to deliver therapy directly into the CSF. This outpatient procedure aims to localize treatment to the affected area while avoiding systemic toxicity.
In addition to scientific milestones, Dr. Hedrick said he regularly makes time to learn about patients’ experiences with the disease, including how it has affected their daily lives and their families.
In addition to scientific milestones, Dr. Hedrick said he regularly makes time to learn about patients’ experiences with the disease, including how it has affected their daily lives and their families.
Challenges in Radiotherapeutic Development
Radiotherapeutic agents introduce several unique development challenges. Chief among them is the supply chain, since these agents lose potency over time due to radioactive decay, quite unlike pills or drug vials, which may have a longer shelf life. This makes manufacturing, distribution and clinical scheduling more complex than for conventional small molecules or biologics.
“You’re fighting the half-life of the radioisotope every day,” Dr. Hedrick noted.
The selection of the radioisotope itself is a key consideration. Plus Therapeutics uses rhenium-186, a beta- and gamma-emitting isotope with a half-life of approximately 90 hours.
Dr. Hedrick noted that the drug can be made to order, shipped in just a few days and remain viable for treatment for another three to four days.
“You can actually recalibrate the radiation because what you’re calculating is a physical property, not so much a chemical property,” he explained. That means clinics can adapt if a surgery is delayed or a patient misses an appointment — “there’s some flexibility at the hospital clinic level to use that same dose to treat the patient.”
He added that this approach supports both clinical usability and economic efficiency, with implications for broader distribution across the US and international markets.
Building a Supportive Network of Collaboration
Advancing radiotherapeutics requires alignment across technology, clinical expertise and infrastructure. Plus Therapeutics has established partnerships with several key organizations, including:
- Brainlab, for imaging and case-planning tools in convection-enhanced delivery
- Telix, SpectronRx, and MURR, for supply chain and radiation services
- MD Anderson, UT Southwestern and UT San Antonio, as clinical trial site partners
CNS cancer care is highly specialized, and the number of neuro-oncologists in the US is relatively small, fewer than 300 nationally, according to Dr. Hedrick.
“We are very reliant on physician leaders who have a heart for these patients,” Dr. Hedrick said. “And the company’s the quarterback in a way for harnessing all these talents and commercial enterprises, physicians, scientists and governments to be able to deliver this. It’s the ultimate orchestration.”
Looking Ahead: Milestones That Matter
Radiotherapeutics have been in clinical use for decades, with radioactive iodine long used to treat thyroid conditions. More recently, targeted therapies in prostate and neuroendocrine cancers have helped validate the potential of this modality in oncology.
Dr. Hedrick noted that these earlier successes provided both a scientific rationale and the necessary infrastructure to pursue a CNS-focused approach.
Plus Therapeutics is currently advancing three clinical programs. In the coming year, the company plans to:
- Complete its Phase II glioblastoma trial — with Phase I data published in Nature Communications — and prepare for potential Phase III
- Launch a dose optimization trial in leptomeningeal metastases
- Begin its pediatric brain cancer trial for ependymoma and high-grade glioma at Lurie Children’s Hospital in Chicago, pending final regulatory alignment
Dr. Hedrick noted that the Phase I leptomeningeal metastases trial showed encouraging early safety and survival signals, which will be further explored in upcoming studies.
In parallel, the company is relaunching a CSF-based diagnostic test platform under a new division, CNSide Diagnostics. This platform is designed to detect tumor cells, assess biomarker expression and help guide therapeutic decision-making for cancers involving the CSF.
In addition to scientific milestones, Dr. Hedrick said he regularly makes time to learn about patients’ experiences with the disease, including how it has affected their daily lives and their families.
“You really don’t get a feel for what the patients are going through and what the clinical need is,” he said, when recalling that he participated in a 5K with a glioblastoma patient.
Overall, with a growing pipeline, a combined therapeutic-diagnostic platform and ongoing clinical collaboration, the company’s efforts reflect tailored approaches to radiation delivery in neuro-oncology.
ABOUT Marc Hedrick
Dr. Marc Hedrick is the President and CEO at Plus Therapeutics, Inc. Previously, Dr. Hedrick served in a number of executive leadership roles including President, CEO and Director at Cytori Therapeutics, Inc., and President and CEO of StemSource, Inc. Dr. Hedrick is a trained general, vascular and plastic surgeon and former Associate Professor of Surgery and Pediatrics at the University of California, Los Angeles (UCLA). Dr. Hedrick also served as Co-Director of the Laboratory of Regenerative Bioengineering and Repair at UCLA.
Dr. Hedrick obtained his MD from the University of Texas Southwestern Medical School, Dallas, and an MBA from The Anderson School at UCLA in 2005.