This cross-cancer proof-of-concept testing study supports the feasibility of applying multimodal AI/radiomics biomarkers to predict treatment response in advanced HR+, HER2- breast cancer, laying the foundation for broader pancancer and pantreatment applications pending further validation.

P1, N=27, Completed, University of Oxford | Active, not recruiting --> Completed

P1, N=133, Completed, Boehringer Ingelheim | Active, not recruiting --> Completed

P1, N=133, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Dec 2023 --> Apr 2024

Mollugin treatment caused obvious decrease in cell viability and proliferation in CRC cells, which were aggravated by ferroptosis inducer erastin and attenuated by ferroptosis inhibitor ferrostatin-1...Further investigation indicated that the IGF2BP3/glutathione peroxidase 4 (GPX4) axis was involved in mollugin-regulated ferroptosis in CRC. In conclusions, Mollugin suppresses proliferation and drives ferroptosis of CRC cells by inhibiting the IGF2BP3/GPX4 axis, suggesting that mollugin may be a potential therapeutic option for CRC.

Xentuzumab plus enzalutamide was tolerable but lacked antitumour activity in unselected patients with mCRPC.

P1, N=133, Active, not recruiting, Boehringer Ingelheim | Trial completion date: Aug 2023 --> Dec 2023

While this study demonstrated that xentuzumab could be safely combined with everolimus and exemestane in patients with HR-positive/HER2-negative advanced breast cancer with non-visceral disease, there was no PFS benefit with the addition of xentuzumab. Trial registration ClinicalTrials.gov, NCT03659136. Prospectively registered, September 6, 2018.

The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression.

We found that inhibition of IGF2BP1 is sufficient to decrease the resistance of chemotherapy-resistant cancer cells with activated Wnt/β-catenin signaling pathway. These findings portray IGF2BP1 as a good candidate for CRC therapy.

Further, LIF treatment enhanced cultured NPC proliferation, which was reduced by picropodophyllin, an IGF-1 receptor inhibitor, even under LIF supplementation. Our findings suggest that IGF expression and release from the NPCs of the fetal cerebrum in fetal CSF is induced by LIF, thus supporting the involvement of the LIF-IGF axis in cerebral cortical development in an autocrine/paracrine manner.

2 million UW-BCC1 cells were injected subcutaneously in the back of 30 immunocompromised mice (Foxn1nu), and they were fed doxycycline supplemented chow. Tumor growth was monitored weekly for eight weeks. Knockdown of IGF2BP1 in UW-BCC1 cells significantly reduced tumor growth in xenograft mice compared to controls (P