Role of Genomic Alterations in HER2 Positive Breast Carcinoma: Focus on Susceptibility and Trastuzumab-therapy

Singla, Heena; Kalra, Sourav; Kheterpal, Preeti; Kumar, Vinod; Munshi, Anjana

doi:10.2174/1568009616666161216094026

Cited by 12 publications

(6 citation statements)

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“…The mass spectra of compounds were established on the Shimadzu LCMS-2010 EV (Maharashtra, India). 1 H NMR and 13 C NMR spectra were recorded at 400 MHz on the FT-Nuclear Magnetic Resonance Spectrometer (FT-NMR), Bruker AVIII, Switzerland using CDCl3 solvent and chemical shift valves were noted in parts per million on δ scale. The coupling constant (J) is denoted in hertz (Hz).…”

Section: Methodsmentioning

confidence: 99%

“…Since most of the currently available chemotherapeutic agents come with multi-drug resistance and acute toxicity. [1] To encounter the future threats arising due to cancer, progressive studies are being conducted towards understanding the biological processes involved in the development of cancer, which may aid in developing more potent and effective anticancer agents for the complete extinction of the disease. [2] Thus, in the pursuit of a more effective anticancer drug, a large number of structurally diverse synthetic and natural products have been explored for their anticancer potential.…”

Section: Introductionmentioning

confidence: 99%

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A Novel Class of Pyrazoline Analogue of Combretastatin-A4 (CA-4): Synthesis Characterization and in-vitro Biological Testing

Shringare

Bhale²,

Chavan³

et al. 2021

Croat. Chem. Acta

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A series of pyrazoline bridged combretastatin analogues were designed and synthesised from their precursor chalcone analogues, and all these compounds were ascertained by IR, 1 H NMR, and mass spectral analysis. Subsequently, all these compounds were evaluated for anticancer activities against breast cancer (MCF-7) and normal Vero (Monkey Kidney) cell lines, and five selected compounds from the series were evaluated against Hela (Human Cervical), MDA-MB-231 (Breast), and A-549 (Lung cancer) cell lines using the Sulforhodamine B (SRB) assay method. Compounds 3a, 6a, 6e, 5b, 7a, 5a, and 7d were found to be the most potent in the series, with a GI50 value of 10 to 30 M in the MCF-7 cell line. Moreover, the same compounds 6a and 7a showed remarkable cytotoxicity against the A-549 (Lung) cell line with a GI50 value ranging from 10 to 30 M, while compound 3a displayed moderate cytotoxicity against the Hela (Human Cervical) cell line. All these compounds were found nontoxic to the Vero (Monkey Kidney) normal cell line.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Class of Pyrazoline Analogue of Combretastatin-A4 (CA-4): Synthesis Characterization and in-vitro Biological Testing

Shringare

Bhale²,

Chavan³

et al. 2021

Croat. Chem. Acta

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“…Breast tumors can involve about 50 copies of the HER2 gene and up to 40- to the 100-fold increase in HER2 protein expression leading to the expression of approximately 2 × 10 6 receptors on the tumor cell surface [ 62 ]. Interestingly, analysis has provided strong evidence that HER2 amplification is accompanied by several undesired biological processes and also could be pronounced as an early event in human breast tumorigenesis [ 77 ]. Nonetheless, enhancement in HER2 expression is detected in nearly half of all in situ ductal carcinomas without any invasiveness [ 62 ].…”

Section: Her2 Overexpression In Human Cancermentioning

confidence: 99%

Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress

et al. 2022

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Due to the overexpression or amplification of human epidermal growth factor receptor 2 (HER2) with poor prognosis in a myriad of human tumors, recent studies have focused on HER2-targeted therapies. Deregulation in HER2 signaling pathways is accompanied by sustained tumor cells growth concomitant with their migration and also tumor angiogenesis and metastasis by stimulation of proliferation of a network of blood vessels. A large number of studies have provided clear evidence that the emerging HER2-directed treatments could be the outcome of patients suffering from HER2 positive breast and also gastric/gastroesophageal cancers. Thanks to its great anti-tumor competence, immunotherapy using HER2-specific chimeric antigen receptor (CAR) expressing immune cell has recently attracted increasing attention. Human T cells and also natural killer (NK) cells can largely be found in the tumor microenvironment, mainly contributing to the tumor immune surveillance. Such properties make them perfect candidate for genetically modification to express constructed CARs. Herein, we will describe the potential targets of the HER2 signaling in tumor cells to clarify HER2-mediated tumorigenesis and also discuss recent findings respecting the HER2-specific CAR-expressing immune cells (CAR T and CAR NK cell) for the treatment of HER2-expressing tumors.

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“…HER2 is a proto‐oncogene also known as neu ‐oncogene which consists of 1255 amino acids and transmembrane glycoprotein (185 KD) that is located on the long arm of the chromosome 17 (17q12). HER2 or ErbB2 is a member of EGFR that regulates the growth and differentiation of cells through several downstream pathways 12 . The HER2 receptor always exists in the form of monomer but when a ligand (HER3, HER4, and HER) binds to its extracellular domain it becomes dimerized causing the transphosphorylation of its intracellular tyrosine kinase domain.…”

Section: Introductionmentioning

confidence: 99%

Human epidermal growth receptor polymorphisms (HER1–rs11543848 and HER2–rs1136201) exhibited significant association with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan

Sombal,

Khan,

Khan

et al. 2024

Health Science Reports

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Background and AimsBreast cancer is the most common type of cancer in women. The genetic polymorphism in HER (HER1–rs11543848 and HER2–rs1136201) were found to be associated with breast cancer risk in different ethnicities worldwide with inconsistent results. The aim of this research study was to evaluate the association of HER1–rs11543848 and HER2–rs1136201 polymorphisms as a risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan.MethodsA total of 314 women including 164 breast cancer patients and 150 age and gender‐matched healthy controls were enrolled from June 2021 to May 2022. All the samples were subjected to DNA extraction followed by Tetra‐ARMS‐PCR for genotyping and gel electrophoresis.ResultsOur results indicated that HER1–rs11543848 risk allele A (p = 0.0001) and heterozygous genotype GA (p = 0.0001) displayed highly significant association with breast cancer, while the homozygous mutant genotype AA indicated association but nonsignificant results (odds ratio [OR] = 2.637, 95% confidence interval [CI] = 1.2258–5.6756, p = 0.0833). Similarly, the HER2–rs1136201 risk allele G (p = 0.0023), the heterozygous genotype AG (p = 0.0530) and homozygous mutant genotype GG showed significant association (OR = 2.5946, 95% CI = 0.9876–6.8165, p = 0.0530) with breast cancer risk. Both the SNPs presented a higher but nonsignificant risk of breast cancer in postmenopausal women (OR = 2.242, p = 0.08 and OR = 2.009, p = 0.06). However, both the SNPs showed significant association (p < 0.005) with family history, metastasis, stage, luminal B, and TNBC.ConclusionIn conclusion, HER1–rs11543848 and HER2–rs1136201 polymorphisms are significantly associated with the higher risk of breast cancer in Pashtun population of Khyber Pakhtunkhwa, Pakistan. These findings advocate for further exploration with larger datasets, offering promising avenues for personalized approaches in breast cancer research and potentially enhancing clinical practices for better risk assessment and targeted management strategies.

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Role of Genomic Alterations in HER2 Positive Breast Carcinoma: Focus on Susceptibility and Trastuzumab-therapy

Abstract: In the current review article, we have summarized the genomic alterations that are responsible for overexpression of HER2 and therefore, increased risk of breast cancer. In addition, the gene variants affecting response towards trastuzumab-therapy have also been discussed.

Cited by 12 publications

References 0 publications

A Novel Class of Pyrazoline Analogue of Combretastatin-A4 (CA-4): Synthesis Characterization and in-vitro Biological Testing

A Novel Class of Pyrazoline Analogue of Combretastatin-A4 (CA-4): Synthesis Characterization and in-vitro Biological Testing

Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor (CAR) for tumor immunotherapy; recent progress

Human epidermal growth receptor polymorphisms (HER1–rs11543848 and HER2–rs1136201) exhibited significant association with breast cancer risk in Pashtun population of Khyber Pakhtunkhwa, Pakistan

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