Receptor tyrosine kinase-like orphan receptor 1: a novel target for cancer immunotherapy

Shabani, Mahdi; Naseri, Jila; Shokri, Fazel

doi:10.1517/14728222.2015.1025753

Cited by 37 publications

(20 citation statements)

References 107 publications

(125 reference statements)

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“…Receptor tyrosine kinase (RTK) pathways have key roles in the progression of various tumors (4–6), with aberrant epidermal growth factor receptor (EGFR) signaling demonstrated to be particularly common (7); EGF family proteins have been revealed to be significantly overexpressed in >60% of tumors (8,9). The main EGF family members include EGFR [also termed human epidermal growth factor receptor 1 (HER1)], HER2 (also termed ErbB2), HER3 (also termed ErbB3) and HER4 (also termed ErbB4).…”

Section: Introductionmentioning

confidence: 99%

Reduction of miR-132-3p contributes to gastric cancer proliferation by targeting MUC13

Liu

Wei

et al. 2017

Molecular Medicine Reports

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Abnormal expression of epidermal growth factor receptor (EGFR) signaling and microRNAs (miRNAs) has been widely seen in gastric cancer. The present study focused on the miRNAs that regulate human epidermal growth factor receptor (HER) activation through mucin 13 (MUC13). The protein level of MUC13 was demonstrated to be significantly increased in gastric cancer tissues compared with normal tissues by western blot analysis and immunohistochemistry. TargetScan bioinformatic predictions indicated that miRNA (miR)-212-3p and miR-132-3p may bind to the 3′-untranslated region of MUC13. Further investigation revealed that miR-132-3p was significantly decreased in gastric cancer tissues compared with normal tissues, whereas miR-212-3p expression was unaffected. Luciferase assays and western blot confirmed MUC13 as a target gene of miR-132-3p. Inhibition of miR-132-3p enhanced gastric cancer cell migration through activation of HER2, extracellular signal-regulated kinase (ERK) and Akt serine/threonine kinase (Akt) signaling, which was a similar effect to that of MUC13 overexpression. In summary, reduction of miR-132-3p may contribute to gastric cancer proliferation by targeting MUC13.

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Section: Introductionmentioning

confidence: 99%

Reduction of miR-132-3p contributes to gastric cancer proliferation by targeting MUC13

Liu

Wei

et al. 2017

Molecular Medicine Reports

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“…ROR1 is a type 1 transmembrane protein expressed on the plasma membrane and has an extracellular domain that is essential for ligand binding and signal transduction . Interestingly, ROR1 is selectively overexpressed in many hematologic malignancies and a number of solid tumors, while it is without significant expression in normal adult tissues . The unique expression profile of ROR1 makes it a promising candidate for novel drug targets, assuming that this expression pattern will maximize effectiveness and minimize off‐target toxicities.…”

Section: Kinase Inhibitors and Cardiac Concernsmentioning

confidence: 99%

“…A monoclonal antibody (cirmtuzumab) was developed by binding to ROR1 on tumor cells and inhibiting Wnt5a signaling, which is a pathway that is important for blocking tumor‐cell proliferation, migration, and survival . The antibody has been used in a phase I clinical trial for chronic lymphocytic leukemia …”

Section: Kinase Inhibitors and Cardiac Concernsmentioning

confidence: 99%

“…is selectively overexpressed in many hematologic malignancies and a number of solid tumors, while it is without significant expression in normal adult tissues. 176,178,179 The unique expression profile of ROR1 makes it a promising candidate for novel drug targets, 176 assuming that this expression pattern will maximize effectiveness and minimize off-target toxicities. A monoclonal antibody (cirmtuzumab) was developed by binding to ROR1 on tumor cells and inhibiting Wnt5a signaling, which is a pathway that is important for blocking tumor-cell proliferation, migration, and survival.…”

Section: Kinase Inhibitors and Cardiac Concernsmentioning

confidence: 99%

“…180 The antibody has been used in a phase I clinical trial for chronic lymphocytic leukemia. 175,178,179,181,182…”

Section: Kinase Inhibitors and Cardiac Concernsmentioning

confidence: 99%

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Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

Zheng

Kros

2017

Medicinal Research Reviews

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To date, five cancer treatment modalities have been defined. The three traditional modalities of cancer treatment are surgery, radiotherapy, and conventional chemotherapy, and the two modern modalities include molecularly targeted therapy (the fourth modality) and immunotherapy (the fifth modality). The cardiotoxicity associated with conventional chemotherapy and radiotherapy is well known. Similar adverse cardiac events are resurging with the fourth modality. Aside from the conventional and newer targeted agents, even the most newly developed, immune‐based therapeutic modalities of anticancer treatment (the fifth modality), e.g., immune checkpoint inhibitors and chimeric antigen receptor (CAR) T‐cell therapy, have unfortunately led to potentially lethal cardiotoxicity in patients. Cardiac complications represent unresolved and potentially life‐threatening conditions in cancer survivors, while effective clinical management remains quite challenging. As a consequence, morbidity and mortality related to cardiac complications now threaten to offset some favorable benefits of modern cancer treatments in cancer‐related survival, regardless of the oncologic prognosis. This review focuses on identifying critical research‐practice gaps, addressing real‐world challenges and pinpointing real‐time insights in general terms under the context of clinical cardiotoxicity induced by the fourth and fifth modalities of cancer treatment. The information ranges from basic science to clinical management in the field of cardio‐oncology and crosses the interface between oncology and onco‐pharmacology. The complexity of the ongoing clinical problem is addressed at different levels. A better understanding of these research‐practice gaps may advance research initiatives on the development of mechanism‐based diagnoses and treatments for the effective clinical management of cardiotoxicity.

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Prolonged hematologic toxicity following treatment with chimeric antigen receptor T cells in patients with hematologic malignancies

et al. 2021

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Chimeric antigen receptor T‐cell therapy (CAR T) is a novel intervention for relapsed/refractory diffuse large B‐cell lymphoma (R/R DLBCL) and other hematologic malignancies. However, it is associated with prolonged hematologic toxicity (PHT) that is unpredictable and can significantly impair patients' quality of life. Reported here is a single‐center experience with PHT in adult patients with R/R DLBCL who received commercial CAR T‐cell therapy between March 1, 2018 and May 30, 2020. Prolonged hematologic toxicity was defined as ≥ grade 3 neutropenia or thrombocytopenia at day +30 after CAR T‐cell therapy. Of the 31 patients identified, 18 patients (58%) developed PHT. Patients with PHT had a shorter 1‐year overall survival (OS) than patients without PHT (36% vs. 81%, P < .05). There were no differences in the median time to ANC recovery for those with PHT compared to patients without PHT (16 days vs. 15 days). Several risk factors were identified to be associated with PHT including CRS (P = .002), receipt of tocilizumab (P = .002) or steroids (P = .033), peak ferritin >5000 ng/ml (P = .048), peak C‐reactive protein (CRP) > 100 mg/L (P = .007), and ferritin greater than the upper limit of normal at day +30. Seven patients with PHT underwent a bone marrow biopsy after CAR T‐cell therapy; all showed complete aplasia or were hypocellular with cellularity ranging from <5% to 10%. These findings identify PHT as a significant toxicity associated with CAR T‐cell therapy and highlight the critical need for further investigations to describe PHT in larger cohorts and identify standards for management of this condition.

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Receptor tyrosine kinase-like orphan receptor 1: a novel target for cancer immunotherapy

Cited by 37 publications

References 107 publications

Reduction of miR-132-3p contributes to gastric cancer proliferation by targeting MUC13

Reduction of miR-132-3p contributes to gastric cancer proliferation by targeting MUC13

Breakthroughs in modern cancer therapy and elusive cardiotoxicity: Critical research‐practice gaps, challenges, and insights

Prolonged hematologic toxicity following treatment with chimeric antigen receptor T cells in patients with hematologic malignancies

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