Molecular perspective on targeted therapy in breast cancer: a review of current status

Cetinkaya, Busra Demir; Avci, Çığır Biray

doi:10.1007/s12032-022-01749-1

Cited by 19 publications

(17 citation statements)

References 109 publications

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“…One example is the development and clinical application of PARP-inhibitor (PARPi); Poly (adenosine diphosphate-ribose) polymerase inhibitors (PARPi) are a key arrow in the oncologist’s quiver among new therapeutics [ 26 , 27 ]. Indeed, PARPi has been found to enhance the clinical outcomes of breast cancer patients with BRCA1/2 germline or somatic mutations, which have been found to improve survival and quality of life [ 28 , 29 , 30 , 31 , 32 ]. As a result, current worldwide guidelines strongly advise BRCA1/2 testing in all patients.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Available Variant Calling Tools for Oxford Nanopore Sequencing in Breast Cancer

Helal¹,

Saad²,

Saad³

et al. 2022

Genes

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The goal of biomarker testing, in the field of personalized medicine, is to guide treatments to achieve the best possible results for each patient. The accurate and reliable identification of everyone’s genome variants is essential for the success of clinical genomics, employing third-generation sequencing. Different variant calling techniques have been used and recommended by both Oxford Nanopore Technologies (ONT) and Nanopore communities. A thorough examination of the variant callers might give critical guidance for third-generation sequencing-based clinical genomics. In this study, two reference genome sample datasets (NA12878) and (NA24385) and the set of high-confidence variant calls provided by the Genome in a Bottle (GIAB) were used to allow the evaluation of the performance of six variant calling tools, including Human-SNP-wf, Clair3, Clair, NanoCaller, Longshot, and Medaka, as an integral step in the in-house variant detection workflow. Out of the six variant callers understudy, Clair3 and Human-SNP-wf that has Clair3 incorporated into it achieved the highest performance rates in comparison to the other variant callers. Evaluation of the results for the tool was expressed in terms of Precision, Recall, and F1-score using Hap.py tools for the comparison. In conclusion, our findings give important insights for identifying accurate variants from third-generation sequencing of personal genomes using different variant detection tools available for long-read sequencing.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Available Variant Calling Tools for Oxford Nanopore Sequencing in Breast Cancer

Helal¹,

Saad²,

Saad³

et al. 2022

Genes

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“…Therefore, developing a novel treatment strategy in addition to conventional therapy is necessary because a treatment protocol, including adjuvant therapy for canine mammary cancer, has not yet been established. Human patients with breast cancer are treated with molecular-targeted drugs using monoclonal antibodies, tyrosine kinase inhibitors, cyclin-dependent kinase 4/6 inhibitors, antiangiogenic agents, and poly (ADP-ribose) polymerase inhibitors in addition to conventional chemotherapy ( 14 ). Molecular-targeted drugs were developed to directly act on molecular cancer cell abnormalities and selectively target various signaling pathways related to cancer cell proliferation, aggression, and apoptosis, and have yielded more successful results in cancer therapy ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

mTOR pathway as a potential therapeutic target for cancer stem cells in canine mammary carcinoma

et al. 2023

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Mammary adenocarcinoma, the most common cancer in female dogs, often exhibits the lymph node and lung metastases and has a higher mortality rate. However, mammary adenocarcinoma has no established treatment, except early surgical excision. Canine mammary carcinoma has many common features with human mammary carcinoma, including clinical characteristics, heterogeneity, and genetic aberrations, making it an excellent spontaneous tumor model for human breast cancer. Diverse cancers comprised heterogeneous cell populations originating from cancer stem cells (CSCs) with self-renewal ability. Therefore, in addition to conventional therapy, therapeutic strategies targeting CSCs are essential for cancer eradication. The present study aimed to extract inhibitors of canine mammary CSCs that suppress their self-renewal ability. Sphere-formation assay, which evaluates self-renewal ability, was performed for the canine mammary cancer cell lines CTBp and CNMp. The spheres formed in this assay were used in inhibitor library screening, which identified various signaling pathways such as proteosome, stress inducer, and mammalian target of rapamycin (mTOR). The present study focused on the mTOR signaling pathway. Western blotting showed higher levels of phosphorylated mTOR in sphere-forming CTBp and CNMp cells than in adherent cells. Drug sensitivity examination using the mTOR inhibitors everolimus and temsirolimus revealed dose-dependent reductions in viability among both sphere-forming cells and adherent cells. Expression of phosphorylated mTOR in adherent and sphere-forming cells decreased by everolimus and temsirolimus treatment. In mice transplanted with CTBp-derived spheres, everolimus treatment significantly decreased tumor volume compared to control. These results reveal that the mTOR signaling pathway may be a potential to be a therapeutic target in both cancer cells and CSCs. Novel therapeutic strategies for canine mammary carcinoma are expected to benefit to human breast carcinoma as well.

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“…Activated pi3k catalyzes the conversion of phosphati-dylinositol-4,-5-bisphosphate (PIP2) to phosphatidylinositol 3,4,5-triphosphate (PIP3). 60 PIP3 then binds to protein kinase B (AKT) containing the pleckstrin homology domain and relocalizes to the internal plasma membrane, resulting in AKT activation. 61 This leads directly or indirectly to the activation of downstream molecular targets such as mammalian target of rapamycin (mTOR), Glycogen synthase kinase-3β (GSK3β), and Forkhead Box Protein O1 (FOXO1).…”

Section: Introductionmentioning

confidence: 99%

“…PI3K is a lipid kinase that can be activated by upstream signals from various receptor tyrosine kinases (RTKs) or G protein‐coupled receptors (GPCRs). Activated pi3k catalyzes the conversion of phosphati‐dylinositol‐4,5‐bisphosphate (PIP2) to phosphatidylinositol 3,4,5‐triphosphate (PIP3) 60 . PIP3 then binds to protein kinase B (AKT) containing the pleckstrin homology domain and relocalizes to the internal plasma membrane, resulting in AKT activation 61 .…”

Section: Introductionmentioning

confidence: 99%

PI3K/AKT/mTOR pathway mediated‐cell cycle dysregulation contribute to malignant proliferation of mouse spermatogonia induced by microcystin‐leucine arginine

Liu

Tian

et al. 2022

Environmental Toxicology

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Environmental cyanotoxin exposure may be a trigger of testicular cancer. Activation of PI3K/AKT/mTOR signaling pathway is the critical molecular event in testicular carcinogenesis. As a widespread cyanotoxin, microcystin-leucine arginine (MC-LR) is known to induce cell malignant transformation and tumorigenesis. However, the effects of MC-LR on the regulatory mechanism of PI3K/AKT/mTOR pathway in seminoma, the most common testicular tumor, are unknown. In this study, mouse spermatogonia cell line (GC-1) and nude mice were used to investigate the effects and mechanisms of MC-LR on the malignant transformation of spermatogonia by nude mouse tumorigenesis assay, cell migration invasion assay, western blot, and cell cycle assay, and so forth. The results showed that, after continuous exposure to environmentally relevant concentrations of MC-LR (20 nM) for 35 generations, the proliferation, migration, and invasion abilities of GC-1 cells were increased by 120%, 340%, and 370%, respectively. In nude mice, MC-LR-treated GC-1 cells formed tumors with significantly greater volume (0.998 ± 0.768 cm 3 ) and weight (0.637 ± 0.406 g) than the control group (0.067 ± 0.039 cm 3 ; 0.094 ± 0.087 g) (P < .05). Furthermore, PI3K inhibitor Wortmannin inhibited the PI3K/AKT/mTOR pathway and its downstream proteins (c-MYC, CDK4, CCND1, and MMP14) activated by MC-LR.Blocking PI3K alleviated MC-LR-induced cell cycle disorder and malignant proliferation, migration and invasive of GC-1 cells. Altogether, our findings suggest that MC-LR can induce malignant transformation of mouse spermatogonia, and the PI3K/ AKT/mTOR pathway-mediated cell cycle dysregulation may be an important target for malignant proliferation. This study provides clues to further reveal the etiology and pathogenesis of seminoma.

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Molecular perspective on targeted therapy in breast cancer: a review of current status

Cited by 19 publications

References 109 publications

Evaluation of the Available Variant Calling Tools for Oxford Nanopore Sequencing in Breast Cancer

Evaluation of the Available Variant Calling Tools for Oxford Nanopore Sequencing in Breast Cancer

mTOR pathway as a potential therapeutic target for cancer stem cells in canine mammary carcinoma

PI3K/AKT/mTOR pathway mediated‐cell cycle dysregulation contribute to malignant proliferation of mouse spermatogonia induced by microcystin‐leucine arginine

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