Threading the needle: Development of Novel MR Methods for Effective Control of an Emerging Lipophilic Tumor Therapy

/ Abstract. Generally, the accepted goal of cancer treatments is the eradication of cancer cells, which in itself will lead to cure. While this has been an effective strategy in some restricted instances, most adult solid cancers remain very difficult to cure and some, like the very malignant glioblastoma, remain exceedingly resistant to this approach despite years of dedicated research. We have been exploring strategies using a different framework of cancer development in which tumors arise as a maladaptive wound response that predicts that cure will not be possible without also focusing on normal tissue healing processes, i.e., tumor cell eradication is not enough. We have identified a prototypical agent, BPM31510, that possesses many of the features that fulfill the necessary requirements for inhibiting cancer while sparing noncancer tissue. This drug, which is composed of CoQ10 incorporated into a lipid nanoemulsion, enables delivery of supraphysiological doses of the highly hydrophobic CoQ10, orders of magnitude greater than are possible with CoQ10 alone. Based on data that is described within, we have demonstrated in vitro that this compound has marked differential effects on glioma cells relative to non-tumor cells and that we can reliably eradicate cancer cells without impeding normal cell growth; we’ve also identified that this effect is exquisitely dose dependent. Our in vivo studies also indicate that we can cure orthotopic glioma implants when this drug is used as a single agent at the correct dose. Our findings could therefore represent a transformative approach to cancer—not only for glioblastoma, but since it is genetically “agnostic”, to other cancers as well. However, a major hurdle in moving towards clinical translation is the lack of an appropriate real time measurement of response, i.e., tumors often grow before they respond, complicating assessment using standard anatomic criteria such as RANO or RECIST. Interestingly, major changes can be identified using noninvasive MR techniques such as proton MRS and deuterium metabolic imaging (DMI) even when MR imaging shows tumor growth, offering an alternative way to measure treatment efficacy. This highly technical proposal, which arises through a longstanding collaboration between a clinical neurooncologist and MRI/MRS engineering group, will offer a roadmap for optimizing three non-invasive imaging techniques, one in general use (proton MRS), one being explored for its clinical utilization (DMI) and one still in experimental development (PROXYL based redox imaging) as measurement tools for this treatment strategy. With their successful completion, our results will be immediately translatable to the clinic and could serve to assess any therapies that use this novel anticancer strategy. Project Number: 1R01CA308814-01 | Fiscal Year: 2026 | NIH Institute/Center: National Cancer Institute (NCI) | Principal Investigator: Daniel Spielman (+1 co-PI) | Institution: STANFORD UNIVERSITY, STANFORD, CA | Award Amount: $593,557 | Activity Code: R01 | Study Section: Emerging Imaging Technologies and Applications Study Section[EITA] View on NIH RePORTER: https://reporter.nih.gov/project-details/11274067