Research
Connecting discoveries, institutions, and patients to accelerate treatments for the rarest cancers.
CIC-rearranged sarcoma and other ultra-rare sarcomas face major research barriers, including small patient populations, limited biological models, fragmented data, and insufficient funding.
Although these diseases are molecularly distinct, patients are often treated with therapies adapted from other cancers because disease-specific evidence and clinical trials remain limited. Progress requires a connected research path:
Understand the Disease
Combine clinical, pathological, and genomic data to better understand treatment response and disease progression.
Identify Therapeutic Vulnerabilities
Use patient-derived models and drug screening to identify biological dependencies that could be targeted.
Translate Discoveries Into Care
Build the evidence and collaboration needed to move promising strategies from preclinical research toward clinical trials.
Rare But Relentless is committed to transforming fragmented discoveries into coordinated progress for CIC-rearranged sarcoma and other overlooked ultra-rare sarcomas.
Research Collaborations & Clinical-Trial Development
Collaboration Is Essential
No single institution encounters enough patients with an ultra-rare cancer to answer every important research question alone.
Progress requires institutions to combine scientific expertise, clinical data, biological models, patient participation, and resources. Rare But Relentless is developing relationships with leading sarcoma institutions to encourage coordinated research and accelerate promising treatment strategies.
FOCUS: CLINICAL RESEARCH AND TRIAL DEVELOPMENT
Memorial Sloan Kettering Cancer Center
STAGE: IN DEVELOPMENT
Rare But Relentless is working with investigators at Memorial Sloan Kettering to explore new treatments for CIC-rearranged sarcoma.
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CIC::DUX4 drives tumor growth by activating abnormal gene transcription. Minnelide disrupts the transcription machinery these cancer cells depend upon, leading to cancer-cell death and reduced tumor growth in preclinical models
Potential clinical path: A small Minnelide pilot for patients with advanced CIC-rearranged sarcoma is in early protocol, funding, regulatory, and operational planning. Not currently open for enrollment.
FOCUS: MINNELIDE AND PRECLINICAL RESEARCH
Duke University
STAGE: ACTIVE PRECLINICAL RESEARCH
Duke researchers developed an advanced genetically engineered model of CIC::DUX4 sarcoma and used it to identify Minnelide as a promising treatment candidate.
- Minnelide demonstrated activity in: CIC::DUX4 sarcoma cells, Genetically engineered mouse models, Human CIC::DUX4 tumor models
Rare But Relentless is helping connect this preclinical work with clinical investigators, institutions, and the drug manufacturer to explore clinical translation.
Potential clinical path: Duke’s findings provide the scientific foundation for the proposed Minnelide pilot.
FOCUS: CLINICAL EXPERTISE AND INTERNATIONAL COLLABORATION
Princess Margaret Cancer Centre
STAGE: COLLABORATION IN DEVELOPMENT
Rare But Relentless is engaging clinical and scientific collaborators within the Princess Margaret sarcoma network.
- Scientific and clinical input into Minnelide trial development, Study design across adolescent and adult patient populations, Potential Canadian research participation, Collaboration across pediatric and adult sarcoma programs, Possible international expansion through established sarcoma networks
Potential clinical path: Princess Margaret collaborators may help inform the proposed Minnelide study and possible future international expansion. Participation as a clinical-trial site has not been finalized.
FOCUS: INTERNATIONAL DATA COLLABORATION AND RESEARCH INFRASTRUCTURE
Sylvester Comprehensive Cancer Center at the University of Miami
STAGE: COLLABORATIVE PLANNING
Rare But Relentless is exploring collaboration with investigators at the University of Miami and the international GRACefUl initiative.
- Consolidating treatment and clinical-outcomes data, Collecting and analyzing genomic information, Connecting additional academic institutions, Supporting prospective patient identification, Developing a coordinated patient-registry model, Collaborating on scientific publications and grant applications, Expanding access to translational models and drug-discovery research
Potential clinical path: This work could help establish the evidence, patient network, and international infrastructure required for future CIC-specific or molecularly guided clinical studies. No resulting CIC-specific trial is currently open.
FOCUS: TUMOR BIOLOGY AND THERAPEUTIC DISCOVERY
Harvard-Affiliated Research Programs
STAGE: ACTIVE RESEARCH
Harvard-affiliated teams are conducting important laboratory and clinical research into CIC-rearranged sarcoma.
- Developing patient-derived tumor models, Studying the biological mechanisms driven by CIC fusion proteins, Conducting CRISPR screening and high-throughput drug testing, Identifying biomarkers and therapeutic vulnerabilities, Evaluating compounds including BTX-A51, Analyzing treatments and results
Potential clinical path: These findings may provide the scientific rationale for future CIC-rearranged sarcoma trials. BTX-A51 is not currently available through a CIC-specific clinical trial.
FOCUS: TARGETED THERAPY
Additional Emerging Treatment Strategy — WEE1 Inhibition
STAGE: TRANSLATIONAL DEVELOPMENT
Research has identified WEE1 as a potential therapeutic vulnerability associated with CCNE1 upregulation in CIC::DUX4 sarcoma. Additional work is needed to determine the best clinical strategy and establish a CIC-specific path to patient testing. No confirmed CIC-specific WEE1 trial is currently open. However, MSK is aiming for a FALL 2026 launch date.
FOCUS: CANCER-CELL SURVIVAL
Additional Emerging Treatment Strategy —MCL-1 Inhibition
STAGE: PRECLINICAL RESEARCH
Patient-derived CIC::DUX4 tumor models have identified MCL-1 as a potential therapeutic vulnerability. MCL-1 is a protein that helps cancer cells avoid programmed cell death. Blocking MCL-1 caused CIC::DUX4 sarcoma cells to die and reduced tumor growth in preclinical models. Similar findings were reported by two independent research groups using patient-derived tumor models.
Potential clinical path: Further research is needed to determine whether MCL-1 inhibitors can be safely and effectively studied in patients with CIC-rearranged sarcoma. No CIC-specific MCL-1 inhibitor trial is currently open.
FOCUS: TARGETING THE CCNE1–CDK2 PATHWAY
Additional Emerging Treatment Strategy —CDK2 Inhibition
STAGE: TRANSLATIONAL RESEARCH
CIC::DUX4 directly increases CCNE1 expression, activating the CCNE1–CDK2 pathway that helps drive cancer-cell growth and division. Preclinical research indicates that this dependence may make CIC::DUX4 sarcoma vulnerable to selective CDK2 inhibitors.
Potential clinical path: The findings support continued development of CDK2-targeted treatment strategies for CIC-rearranged sarcoma. No CIC-specific CDK2 inhibitor trial is currently open.
Connect Research Teams
Bring together investigators and institutions that may otherwise be working independently.
Advance Clinical Trials
Connect preclinical discoveries with investigators, institutions, biotechnology companies, and potential trial sites.
Identify Funding
Pursue philanthropic support, research grants, and partnerships for projects that may not receive traditional funding.
Our Role
How Rare But Relentless Accelerates Research
Build the Patient Network
Help researchers reach patients affected by cancers too rare for any institution to study alone.
Support Data Collaboration
Encourage responsible sharing and consolidation of clinical, genomic, and patient-outcomes data.
Keep Patients Involved
Ensure that patient needs, experiences, and urgency remain central to research priorities.
Collaborate With Us
We welcome conversations with researchers, clinicians, biotechnology companies, academic institutions, advocacy organizations, patients, and families committed to advancing treatments for CIC-rearranged and other ultra-rare sarcomas.
Help Us Turn Research Into Treatment
Research initiatives and potential clinical trials described on this page remain subject to scientific review, funding, regulatory approval, and institutional authorization. A project described as being in development is not currently open for enrollment. Inclusion of an institution does not imply its endorsement of Rare But Relentless Foundation. Patients should consult their treating physicians and ClinicalTrials.gov for currently available studies.