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| http://dx.doi.org/10.1200/PO.22.00697 | DOI Listing |
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If it is a solid tumor target, then it may be a hematologic cancer target: Bridging the great divide.
Med
December 2024
Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI, USA; WIN Consortium, Paris, France; University of Nebraska, Omaha, NE, USA. Electronic address:
Tumor-agnostic US Food and Drug Administration approvals are transforming oncology. They include larotrectinib/entrectinib/repotrectinib (NTRK fusions), selpercatinib (RET fusions), dabrafenib/trametinib (BRAF 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.
View Article and Find Full Text PDFRepotrectinib: a promising new therapy for advanced nonsmall cell lung cancer.
Ann Med Surg (Lond)
December 2024
Dow University of Health Sciences (DUHS), Karachi, Pakistan.
Nonsmall cell lung cancer (NSCLC) is the major cause of cancer-related mortality worldwide, accounting for 84% of lung cancer cases. The newly FDA-approved kinase inhibitor, repotrectinib (AUGTYRO), offers a promising option for treating advanced or metastatic NTRK/ROS1-positive Nonsmall cell lung cancer. Repotrectinib has demonstrated significant efficacy in clinical trials.
View Article and Find Full Text PDFTissue-Agnostic Targeting of Neurotrophic Tyrosine Receptor Kinase Fusions: Current Approvals and Future Directions.
Cancers (Basel)
October 2024
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
fusions are oncogenic drivers for multiple tumor types. Therefore, the development of selective tropomyosin receptor kinase (TRK) inhibitors, including larotrectinib and entrectinib, has been transformative in the context of clinical management, given the high rates of responses to these drugs, including intracranial responses in patients with brain metastases. Given their promising activity in pan-cancer cohorts, larotrectinib and entrectinib received U.
View Article and Find Full Text PDFRepotrectinib: Redefining the therapeutic landscape for patients with ROS1 fusion-driven non-small cell lung cancer.
Clin Transl Med
October 2024
Department of Medicine, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Article Synopsis
- The ROS1 proto-oncogene is linked with receptor tyrosine kinases and plays a significant role in treating ROS1 fusion-positive non-small cell lung cancer (NSCLC) using FDA-approved TKIs like crizotinib and entrectinib, though these medications face challenges such as resistance and limited brain penetration.
- Repotrectinib, a new macrocyclic TKI, was created to tackle resistance mutations and enhance brain distribution, showing strong effectiveness in the TRIDENT-1 trial with high response rates in both TKI-naïve and TKI-pretreated patients.
- The trial showed that 79% of TKI-naïve patients achieved an objective response and had longer progression
CTLA4 blockade abrogates KEAP1/STK11-related resistance to PD-(L)1 inhibitors.
Nature
November 2024
Department of Thoracic and Head and Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Article Synopsis
- Dual immune checkpoint blockade (ICB) using CTLA4 and PD-(L)1 inhibitors shows improved anti-tumor effectiveness and immune toxicity compared to PD-(L)1 inhibitors alone in advanced non-small-cell lung cancer (NSCLC) patients.
- Patients with mutations in STK11 and/or KEAP1 genes benefit more from the combination treatment compared to those receiving only PD-(L)1 inhibitors, as shown in the POSEIDON trial.
- The loss of KEAP1 serves as a strong predictor for the success of dual ICB, as it leads to a more favorable outcome by changing the tumor's immune environment to better engage CD4 and CD8 T cells for anti-tumor activity. *
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