Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

Rivera-Franco, Mónica M.; Rodríguez, Eucario León; Benítez, Braulio Martínez; Rodriguez, Lourdes; González, María de la Luz Sevilla; Alonso, Alejandra Armengol

doi:10.4137/bcbcr.s40934

Cited by 3 publications

(1 citation statement)

References 55 publications

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“…As we previously mentioned, it is essential to develop new selective and effective inhibitors of PTP1B to treat PTP1B-related diseases, such as T2DM, obesity, lymphoma, and breast cancer [35,[43][44][45][46][47][48][49]. However, PTPs are highly conserved, making the development of such inhibitors challenging.…”

Section: Newly Developed Specific Ptp1b Inhibitorsmentioning

confidence: 99%

Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives

Liu

Mathieu²,

Berthelet

et al. 2022

IJMS

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Phosphorylation is an essential process in biological events and is considered critical for biological functions. In tissues, protein phosphorylation mainly occurs on tyrosine (Tyr), serine (Ser) and threonine (Thr) residues. The balance between phosphorylation and dephosphorylation is under the control of two super enzyme families, protein kinases (PKs) and protein phosphatases (PPs), respectively. Although there are many selective and effective drugs targeting phosphokinases, developing drugs targeting phosphatases is challenging. PTP1B, one of the most central protein tyrosine phosphatases (PTPs), is a key player in several human diseases and disorders, such as diabetes, obesity, and hematopoietic malignancies, through modulation of different signaling pathways. However, due to high conservation among PTPs, most PTP1B inhibitors lack specificity, raising the need to develop new strategies targeting this enzyme. In this mini-review, we summarize three classes of PTP1B inhibitors with different mechanisms: (1) targeting multiple aryl-phosphorylation sites including the catalytic site of PTP1B; (2) targeting allosteric sites of PTP1B; (3) targeting specific mRNA sequence of PTP1B. All three types of PTP1B inhibitors present good specificity over other PTPs and are promising for the development of efficient small molecules targeting this enzyme.

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Section: Newly Developed Specific Ptp1b Inhibitorsmentioning

confidence: 99%

Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives

Liu

Mathieu²,

Berthelet

et al. 2022

IJMS

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Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

Sunzini

Stefano

Chimenti

et al. 2020

IJMS

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The social and economic impact of chronic inflammatory diseases, such as arthritis, explains the growing interest of the research in this field. The antioxidant and anti-inflammatory properties of the endogenous gasotransmitter hydrogen sulfide (H 2 S) were recently demonstrated in the context of different inflammatory diseases. In particular, H 2 S is able to suppress the production of pro-inflammatory mediations by lymphocytes and innate immunity cells. Considering these biological effects of H 2 S, a potential role in the treatment of inflammatory arthritis, such as rheumatoid arthritis (RA), can be postulated. However, despite the growing interest in H 2 S, more evidence is needed to understand the pathophysiology and the potential of H 2 S as a therapeutic agent. Within this review, we provide an overview on H 2 S biological effects, on its role in immune-mediated inflammatory diseases, on H 2 S releasing drugs, and on systems of tissue repair and regeneration that are currently under investigation for potential therapeutic applications in arthritic diseases.

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ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab

et al. 2019

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Trastuzumab has markedly improved the treatment and long-term prognosis of patients with HER2-positive breast cancer. A frequent clinical challenge in patients with relapsing and/or metastatic disease is de novo or acquired trastuzumab resistance, and to date no predictive biomarkers for palliative trastuzumab have been established. In the present study, the prognostic values of factors involved in the HER2-associated PI3K/Akt signalling pathway were explored. The first 46 consecutive patients treated at the Department of Oncology, Linköping University Hospital between 2000 and 2007 with trastuzumab for HER2-positive metastatic breast cancer were retrospectively included. The gene copy number variation and protein expression of several components of the PI3K/Akt pathway were assessed in the tumour tissue and biopsy samples using droplet digital polymerase chain reaction and immunohistochemistry. Patients with tumours displaying a high-grade ERBB2 (HER2) amplification level of ≥6 copies had a significantly improved overall survival hazard ratio [(HR)=0.4; 95%, confidence interval (CI): 0.2–0.9] and progression-free survival (HR=0.3; 95% CI: 0.1–0.7) compared with patients with tumours harbouring fewer ERBB2 copies. High-grade ERBB2 amplification was significantly associated with the development of central nervous system metastases during palliative treatment. Copy gain (≥3 copies) of the gene encoding the tyrosine phosphatase PTPN2 was associated with a shorter overall survival (HR=2.0; 95% CI: 1.0–4.0) and shorter progression-free survival (HR=2.1; 95% CI: 1.0–4.1). In conclusion, high ERBB2 amplification level is a potential positive prognostic factor in trastuzumab-treated HER2-positive metastatic breast cancer, whereas PTPN2 gain is a potential negative prognostic factor. Further studies are warranted on the role of PTPN2 in HER2 signalling.

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Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

Cited by 3 publications

References 55 publications

Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives

Human Protein Tyrosine Phosphatase 1B (PTP1B): From Structure to Clinical Inhibitor Perspectives

Hydrogen Sulfide as Potential Regulatory Gasotransmitter in Arthritic Diseases

ERBB2 and PTPN2 gene copy numbers as prognostic factors in HER2‑positive metastatic breast cancer treated with trastuzumab

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