The goal of this clinical research study is to learn if the combination of brigatinib and either local consolidation therapy (such as radiotherapy or surgery) or chemotherapy (pemetrexed and carboplatin) can help to control the disease compared with brigatinib alone. The safety of these combinations will also be studied.

Start Date11 Dec 2024

Sponsor / Collaborator

The University of Texas MD Anderson Cancer Center

100 Clinical Results associated with IGF-1R x ALK

100 Translational Medicine associated with IGF-1R x ALK

0 Patents (Medical) associated with IGF-1R x ALK

Literatures (Medical) associated with IGF-1R x ALK

01 Oct 2024·Thyroid®

TG-IGF1R: A Novel Receptor Tyrosine Kinase Fusion Oncogene in Pediatric Thyroid Cancer

Article

Author: Franco, Aime T. ; Ricarte-Filho, Julio C. ; Bauer, Andrew J. ; Isaza, Amber ; Hinkle, Kyle ; Reichenberger, Erin R.

Background: Receptor tyrosine kinase (RTK) fusions of RET, NTRK1/3, and ALK are enriched among pediatric thyroid cancer patients with metastatic and persistent disease, and their oncoproteins represent attractive drug targets. Methods: We performed RNA-sequencing in a papillary thyroid cancer (PTC) lacking other frequent driver alterations. Results: We report a novel RTK fusion, TG-insulin-like growth factor 1 receptor gene (IGF1R), in a 17-year-old female patient with angioinvasive follicular variant PTC. The in-frame fusion protein preserves the cholinesterase-like domain of TG with dimerization properties and the transmembrane and kinase domain of IGF1R. The tumor sample shows increased IGF1R mRNA expression and tyrosine kinase phosphorylation, augmentation of Mitogen activated protein kinase (MAPK) transcriptional output genes, and decreased NIS levels. Conclusions: We reveal a novel targetable kinase fusion oncogene in thyroid cancer which is not incorporated in different thyroid-specific sequencing panels. The integration of IGF1R fusion screening in the next versions of thyroid-specific targeted next-generation sequencing panels may be beneficial to thyroid cancer patients.

05 Jul 2023·EMBO reports

LTK and ALK promote neuronal polarity and cortical migration by inhibiting IGF1R activity

Article

Author: Liu, Ying ; Ho, Stephanie Ky ; Attisano, Liliana ; Gill, Mandeep ; Christova, Tania

AbstractThe establishment of axon‐dendrite polarity is fundamental for radial migration of neurons, cortical patterning, and formation of neuronal circuits. Here, we show that the receptor tyrosine kinases, Ltk and Alk, are required for proper neuronal polarization. In isolated primary mouse embryonic neurons, the loss of Ltk and/or Alk causes a multiple axon phenotype. In mouse embryos and newborn pups, the absence of Ltk and Alk delays neuronal migration and subsequent cortical patterning. In adult cortices, neurons with aberrant neuronal projections are evident and axon tracts in the corpus callosum are disrupted. Mechanistically, we show that the loss of Alk and Ltk increases the cell‐surface expression and activity of the insulin‐like growth factor 1 receptor (Igf‐1r), which activates downstream PI3 kinase signaling to drive the excess axon phenotype. Our data reveal Ltk and Alk as new regulators of neuronal polarity and migration whose disruption results in behavioral abnormalities.

01 May 2023·Redox Biology

Inhibiting SCD expression by IGF1R during lorlatinib therapy sensitizes melanoma to ferroptosis

Article

Author: Zhou, Qian ; Liu, Hong ; Zeng, Furong ; Chen, Xiang ; Ye, Lin ; Deng, Guangtong ; Zhang, Yilei ; He, Yi

Induction of ferroptosis is an emerging strategy to suppress melanoma progression. Strategies to enhance the sensitivity to ferroptosis induction would be a major advance in melanoma therapy. Here, we used a drug synergy screen that combined a ferroptosis inducer, RSL3, with 240 anti-tumor drugs from the FDA-approved drug library and identified lorlatinib to synergize with RSL3 in melanoma cells. We further demonstrated that lorlatinib sensitized melanoma to ferroptosis through inhibiting PI3K/AKT/mTOR signaling axis and its downstream SCD expression. Moreover, we found that lorlatinib's target IGF1R, but not ALK or ROS1, was the major mediator of lorlatinib-mediated sensitivity to ferroptosis through targeting PI3K/AKT/mTOR signaling axis. Finally, lorlatinib treatment sensitized melanoma to GPX4 inhibition in preclinical animal models, and melanoma patients with low GPX4 and IGF1R expression in their tumors survived for longer period. Altogether, lorlatinib sensitizes melanoma to ferroptosis by targeting IGF1R-mediated PI3K/AKT/mTOR signaling axis, suggesting that combination with lorlatinib could greatly expand the utility of GPX4 inhibition to melanoma patients with IGF1R-proficient expression.

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