Anaplastic lymphoma kinase (ALK) alterations in non-small cell lung cancer (NSCLC) can be effectively treated with a variety of ALK-targeted drugs. After the approval of the first-generation ALK inhibitor crizotinib which achieved better results in prolonging the progression-free survival (PFS) compared with chemotherapy, a number of next-generation ALK inhibitors have been developed including ceritinib, alectinib, brigatinib, and ensartinib. Recently, a potent, third-generation ALK inhibitor, lorlatinib, has been approved by the Food and Drug Administration (FDA) for the first-line treatment of ALK-positive (ALK+) NSCLC. These drugs have manageable toxicity profiles. Responses to ALK inhibitors are however often not durable, and acquired resistance can occur as on-target or off-target alterations. Studies are underway to explore the mechanisms of resistance and optimal treatment options beyond progression. Efforts have also been undertaken to develop further generations of ALK inhibitors. This review will summarize the current situation of targeting the ALK signaling pathway.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9020874 | PMC |
| http://dx.doi.org/10.3389/fonc.2022.863461 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Spectrum and carcinogenic properties of thyroglobulin gene fusions in thyroid.
Endocr Relat Cancer
January 2025
A Nikitski, Department of Pathology, University of Pittsburgh, Pittsburgh, 15261, United States.
Approximately 10-20% of thyroid cancers are driven by gene fusions, which activate oncogenic signaling through aberrant overexpression, ligand-independent dimerization, or loss of inhibitory motifs. We identified 13 thyroid tumors with thyroglobulin (TG) gene fusions and aimed to assess their histopathology and the fusions' oncogenic and tumorigenic properties. Of 11 cases with surgical pathology, 82% were carcinomas and 18% noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP).
View Article and Find Full Text PDFBone morphogenetic protein-4 induced matrix turnover and osteogenic differentiation-related molecules of stem cells from apical papilla and its associated ALK/Smad signaling.
J Dent Sci
January 2025
School of Dentistry, College of Medicine, National Taiwan University, Taipei, Taiwan.
Background/purpose: Revascularization procedures are used over apexification to treat teeth with necrotic pulp tissues and incomplete root formation. Clinically, inducing proliferation, migration, matrix deposition, and differentiation of stem cells from apical papilla (SCAPs) are critical for pulp regeneration. The study aimed to elucidate the impact of bone morphogenetic protein-4 (BMP-4) on plasminogen activation molecules and the osteogenic/odontogenic differentiation of SCAPs, as well as understand the related signaling mechanisms.
View Article and Find Full Text PDFIntroduction: We present a case of a 9-year-old girl diagnosed with a myeloproliferative neoplasm (MPN) harboring both monosomy 7 and an ALK/ROS1 fusion gene.
Case Presentation: The neoplasm was resistant to conventional AML chemotherapy and required hematopoietic cell transplantation (HCT) to achieve remission.
Discussion: MPNs with monosomy 7 and ALK/ROS1 fusions occur in a wide age range of children and adults, and require HCT for long-term remission.
Recurrent Poorly Differentiated Thyroid Cancer Successfully Treated With Radiation and Immunotherapy.
JCEM Case Rep
February 2025
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer, Houston, TX 77030, USA.
A 65-year-old patient presented with recurrent, locally advanced poorly differentiated thyroid cancer despite 2 neck surgeries, and with newly diagnosed brain and skull base metastases. He was treated with palliative stereotactic radiosurgery to the brain and skull base lesions. Thereafter, as no targetable genetic alteration was identified and antiangiogenic multikinase inhibitors were deemed at high risk of hemorrhagic complications, off-label systemic therapies were considered.
View Article and Find Full Text PDFLorlatinib Induced Blindness: A Rare Entity.
Pract Radiat Oncol
January 2025
Department of Radiation Oncology, Acibadem Mehmet Ali Aydinlar University School of Medicine, Istanbul, Turkey. Electronic address:
Lorlatinib is a central nervous system (CNS) penetrant third generation tyrosine kinase inhibitor (TKI) approved for the first line management of metastatic non-small cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK) rearrangement [1] which accounts for 3-5% of NSCLC cases [2]. The most commonly reported side effects include hyperlipidemia, edema, peripheral neuropathy and CNS effects [2]. While ocular side effects such as photopsia, blurred vision, vitreous floaters and diplopia have been documented with another ALK TKI, crizotinib, there are few reports of such effects with lorlatinib [3].
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!