ALK-driven tumors and targeted therapy: focus on crizotinib

The prognosis of the primary refractory anaplastic lymphoma kinase (ALK+) anaplastic T large cell lymphoma is ominous. The identification of molecular targets with potential to drive oncogenesis remains a cornerstone for the designing of new selective cancer therapies. Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer with rearrangements on ALK gene. The reported cases describe the use of crizotinib as a bridging strategy prior to allotransplantation; there are no reported prolonged survivals under monotherapy with Crizotinib. We report a case of a primary refractory ALK+ anaplastic large-cell lymphoma that sustains complete response after 3 years of crizotinib monotherapy.

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“…Crizotinib is a selective ATP-competitive inhibitor for ALK, approved for its use in lung cancer harboring rearrangements on ALK gene. 3 …”

Section: Introductionmentioning

confidence: 99%

Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib

et al. 2016

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“… 29 – 31 Anaplastic lymphoma kinase inhibitor crizotinib was largely confined to an adenocarcinoma subtype. 32 Upregulation of the FGF2 and FGFR3 genes in an established xenograft model possessing acquired resistance to bevacizumab was reported, while inhibition of the FGFR in resistant tumors led to the restoration of sensitivity to bevacizumab. 33 There is a paucity of personalized targeting treatment of squamous lung cancer, which constitutes the major histology type of NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Basic fibroblast growth factor shows prognostic impact on survival in operable non‐small cell lung cancer patients

Gao

et al. 2014

Thoracic Cancer

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BackgroundThe important role of angiogenesis displaying in tumor development and metastasis has been generally realized. Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) and endostatin (ES) are critical members of angiogenesis modulating the balance between pro-angiogenenic and anti-angiogenenic factors. The aim of this study was to evaluate the circulating level of these factors in serum and explore their prognostic significance in 96 operable non-small cell lung cancer (NSCLC) patients.MethodsPre-operational serum VEGF, bFGF, and ES were determined by commercially available enzyme-link immunosorbent assay for 96 NSCLC patients and compared to a cohort of healthy controls (n = 51). Values were correlated with clinicopathological features and overall survival (OS).ResultsThe pretreatment serum levels of VEGF, bFGF and ES in NSCLC were significantly higher than in the healthy control (P < 0.001, P = 0.009 and P = 0.016, respectively). Univariate survival analysis showed that a high bFGF level correlated with shorter OS and remained an independent factor in multivariate analysis (hazard ratio [HR] = 1.918, 95% confidence interval [CI], 1.061–3.464). In the squamous subtype, a high bFGF indicated a particularly poor prognosis (HR = 2.609, 95% CI, 1.188–5.729).ConclusionsbFGF is an independent predictor of poor survival in patients with NSCLC. For patients with high serum bFGF, aggressive antitumor treatments should be given after surgery. Approaches targeting the bFGF signaling pathway should be considered as potentially promising therapeutic strategies in NSCLC, especially for the squamous subtype.

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“…As a final consideration, it is recommended, for treatment, the resection of the tumor, if possible, an association with corticosteroids, chemotherapy or radiotherapy, is also preconized. There are studies undergoing for the use of Crizotinib for IMT with positive ALK rearrangement [3].…”

Section: Introductionmentioning

confidence: 99%

ALK Negative Inflammatory Myofibroblastic Tumor Synchronous with Classical Hodgkin Lymphoma

Sandoval

França²,

Sanmartino³

et al. 2019

Case Rep Oncol

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Inflammatory myofibroblastic tumor or inflammatory pseudotumor was first described by Brunn in 1932. Umiker et al. named it so in 1954 for its ability to mimic malignancy clinically and radiologically [Med Pediatr Oncol 2000; 35(5): 484–7]. This tumor, characterized by its rareness, affects mainly the lung and the orbit. Histologically, the tumor is characterized by the presence of fibroblasts, myofibroblasts, polymorphs, lymphocytes, and neutrophils. This case report and review of literature present a male patient, 37 years old, with a bulky mediastinal lesion at the topography of the 4th rib. Histopathology reveals Hodgkin’s Lymphoma (HL) concomitant with inflammatory myofibroblastic tumor (IMT). This report aims to emphasize the relevance of differential diagnoses to a better medical assistance. To the best of our knowledge, a case with this characteristic has never been seen before.

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ALK-driven tumors and targeted therapy: focus on crizotinib

Cited by 12 publications

References 102 publications

Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib

Three Years Sustained Complete Remission Achieved in a Primary Refractory ALK-Positive Anaplastic T Large Cell Lymphoma Treated with Crizotinib

Basic fibroblast growth factor shows prognostic impact on survival in operable non‐small cell lung cancer patients

ALK Negative Inflammatory Myofibroblastic Tumor Synchronous with Classical Hodgkin Lymphoma

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