tasquinimod (ABR-215050)

P1/2, N=33, Recruiting, M.D. Anderson Cancer Center | Active, not recruiting --> Recruiting

This finding suggests that tasquinimod, an S100A9 inhibitor, could be a viable therapeutic option. Furthermore, the interaction between MMP11 and COL16A1 in stroma-rich regions suggests that cancer-associated fibroblasts may contribute to improved outcomes. Our study underscores the critical role of spatial gene expression analysis in elucidating the tumor microenvironment and its impact on prognosis in patients undergoing E+L treatment, thereby opening new avenues for targeted interventions.

P1/2, N=1, Active, not recruiting, M.D. Anderson Cancer Center | Phase classification: P2 --> P1/2

Blocking S100a9 with tasquinimod rescues the defects of Sucnr1 knock-out mice, and combined with a potent Sucnr1 agonist shows therapeutic value in AML mice...Together, Sucnr1 signaling restricts hematopoiesis at least partially through HSPC and via control of S100a8/S100a9. Its dysregulation emerges as contributor to malignancy that opens therapeutic avenues for AML patients.

For comparison, the clinically investigated antimetastatic agent tasquinimod showed moderate activity in 4T1 cells (IC50 = 180.7 μM), serving as a pharmacological benchmark. Notably, despite 4T1's ER-negative status, 1A4HP suppressed cell growth, suggesting possible ER-independent or off-target mechanisms, similar to tamoxifen's secondary effects. Collectively, these results identify 1A4HP as a promising lead compound for further exploration in breast cancers.

FB2 also reduced the rate of microtubule regrowth in cells; however, we are unable to conclude whether this is due to direct binding to tubulin or to some indirect mechanism involving initial interaction with some other target sites. These effects on tubulin dynamics are likely responsible for defects in spindle structure, mitotic arrest, and the observed robust killing of cancer cells.

Furthermore, tasquinimod treatment alone or combined with cisplatin significantly enhanced tumor infiltration of activated CD8+ (CD69-positive) T cells. Overall, our results, for the first time, show that S100A9 enhances SCLC progression and metastasis by altering the tumor microenvironment, and its inhibition using tasquinimod alone or in combination with chemotherapy could be developed as a promising therapeutic strategy for SCLC.

P1, N=30, Terminated, University of Pennsylvania | Trial completion date: Jul 2026 --> Jul 2025 | Active, not recruiting --> Terminated; Slow accrual at the time when sufficient participants were already enrolled to answer the scientific question posed by the study.

The alarmins, S100A8 (A8) and S100A9 (A9), are low molecular weight proteins belonging to the S100 protein family. Notably, cotreatment with TQ and ruxolitinib or OTX015 induced significantly greater survival than treatment with single agents in the NSG mice engrafted with the PDX cells. These findings clearly demonstrate the preclinical efficacy of TQ in advanced MPN-BP cells and create the rationale to further interrogate the efficacy of TQ-based combinations with the current, front-line therapies or novel agents in advanced MPNs with excess blasts.

We previously demonstrated that tasquinimod ameliorates the MPN phenotype, reducing splenomegaly and normalizing fibrosis in a JAK2V617F-driven preclinical model...Our data highlight the hematopoietic origin of the inflammatory signals driving fibrosis. These insights pave the way for potential therapeutic strategies targeting inflammatory signaling pathways in MPN to mitigate fibrosis and improve patient outcomes.

P2, N=1, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=33 --> 1

Our study reveals that S100A9 facilitates immune evasion in HCC by enhancing PARP1 ubiquitination, STAT3 phosphorylation, and PD-L1 expression. Furthermore, combining S100A9 inhibitors with anti-PD-1 antibodies markedly enhances the therapeutic efficacy of ICIs in HCC. These findings highlight S100A9 as a potential therapeutic target for overcoming resistance to immunotherapy in HCC.