FGFR1 expression

They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAFV600E mutations), pembrolizumab/dostarlimab (microsatellite instability), pembrolizumab (high tumor mutational burden), and trastuzumab deruxtecan (HER2 3+ expression) (all solid cancers). Pemigatinib is approved for FGFR1-rearranged myeloid/lymphoid neoplasms...For example, BRAFV600E and IDH1/2 mutations; ALK, FGFR, and NTRK fusions; PD-L1 amplification; and CD70 antigens are druggable in both solid and blood malignancies by gene-/immune-targeted therapies/chimeric antigen receptor T cells. Future biomarker-based tissue-agnostic basket studies/approvals should bridge the great divide and include both solid and hematologic cancers.

We developed a novel new squamous cell lung carcinoma cell line, OMUL-1, that expresses IGF1R and PD-L1.

[68Ga]Ga-DOTA-FGFR1 PET/CT had higher specificity than [18F]FDG PET/CT for the detection of primary lung cancer. In addition, [68Ga]Ga-DOTA-FGFR1 PET/CT also had higher diagnostic accuracy, specificity, and NPV for lymph node metastasis, but its diagnostic sensitivity for metastatic lesions was lower than [18F]FDG PET/CT. Therefore, [68Ga]Ga-DOTA-FGFR1 can be used as an effective supplement to [18F]FDG to a certain extent.

Part 1 included treatment with fulvestrant (FUL) 500 mg + E7090 (105 or 140 mg) or exemestane (EXE) 25 mg + E7090 (105 or 140 mg). These results emphasize that FGFR pathway activation evaluated with mRNA expression of selected genes at BL—rather than FGFR gene abnormalities—is a key molecular determinant for sensitivity to E7090, an FGFR inhibitor. Future validation of these biomarkers is necessary in a larger population of people with ER+/HER2− BC.

Herein, a hydrogelator, Nap-Phe-Phe-Phe-Glu-Thr-Glu-Leu-Tyr-OH (Nap-Y), was rationally designed to coassemble with an FGFR1 inhibitor nintedanib (Nin) to form a peptide hydrogel Gel Y/Nin for localized administration and FGFR1-triggered release of Nin...Nude mouse studies show that Gel Y/Nin exhibits enhanced therapeutic efficacy on lung tumor than free Nin. We anticipate that Gel Y/Nin will be utilized for lung cancer treatment in clinical settings in the near future.

In addition, we showed that cells obtained by long-term exposure to taltobulin are resistant to both taltobulin and other microtubule-targeting drugs, and exhibit elevated levels of FGFR1 and cyclin D. We also found that the presence of FGF-ligand trap prevents the development of long-term resistance to taltobulin. Our results shed light on how blocking the FGF1/FGFR1 axis by honokiol and FGF ligand trap could help develop more effective cancer therapies, potentially preventing the emergence of drug-resistant relapses.

P1, N=37, Completed, Bayer | Active, not recruiting --> Completed

In vitro, the combination of nivolumab and OM-RCA-01 resulted in higher levels of interferon gamma and interleukin-2 release compared with nivolumab alone. In vivo, pembrolizumab in combination with OM-RCA-01 produced a greater inhibitory effect on tumor growth compared with vehicle and pembrolizumab alone...Combining an anti-FGFR1 antibody with a checkpoint inhibitor may enhance the efficacy of both drugs. However, further studies are needed to elucidate the mechanism of this interaction.

This also resulted in significant synergy between BGJ 398 and VEGFR inhibitors (i.e., sunitinib and regorafenib) by enhancing their pro-apoptotic and anti-proliferative activities. Mechanistically, the FGF2-induced activation of the FGFR pathway turns on VEGFR signaling via the overproduction of VEGF-A, induces the interaction between FGFR1/2 and VEGFR1, and thereby renders cancer cells highly sensitive to the dual inhibition of the aforementioned RTKs. Thus, our data uncovers the novel mechanism of the cross-talk between the aforementioned RTKs in IM-resistant GISTs lacking secondary KIT mutations and suggests that the dual blockade of FGFR and VEGFR signaling might be an effective treatment strategy for patients with GIST-acquired IM resistance via KIT-independent mechanisms.

In breast cancer, the 8p11.2-p12 amplicon shows clinically relevant gene expression profiles which could serve as potential targets for precision medicine in breast cancer patients. Moreover, the identified 7-gene minimal amplicon could be used as prognostic predictor for long-term survival.

Hence, the results provide insights into the molecular interaction responsible for the anti-breast cancer capabilities of mono-chalcone compounds. The online version contains supplementary material available at 10.1007/s13205-024-03991-y.

We have defined specific leukemia responsive neutrophil subgroups based on their unique gene expression profile, which appear to be the precursors of neutrophils specifically associated with leukemia progression. An important event during development of these neutrophils is upregulation MMP genes which facilitated mobilization of these precursors from the BM in response to cancer progression, suggesting a possible therapeutic approach to suppress the development of immune tolerance.