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PIM1/STAT3 axis: a potential co-targeted therapeutic approach in triple-negative breast cancer

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Abstract

Triple-negative breast cancer lacks an expression of ER, PR, and Her-2, has a poor prognosis, and there are no target therapies available. Therapeutic options to treat TNBC are limited and urgently needed. Strong evidence indicates that molecular signaling pathways have a significant function to regulate biological mechanisms and their abnormal expression endows with the development of cancer. PIM kinase is overexpressed in various human cancers including TNBC which is regulated by various signaling pathways that are crucial for cancer cell proliferation and survival and also make PIM kinase as an attractive drug target. One of the targets of the STAT3 signaling pathway is PIM1 that plays a key role in tumor progression and transformation. In this review, we accumulate the current scenario of the PIM-STAT3 axis that provides insights into the PIM1 and STAT3 inhibitors which can be developed as potential co-inhibitors as prospective anticancer agents.

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Abbreviations

4EBP-1:

Eukaryotic initiation factor 4E-binding protein 1

AMPK:

AMP-activated protein kinase

CBP:

CREB-binding protein

EGF:

Epidermal growth factor

eIF-2α:

Eukaryotic initiation factors 2α

ER:

Estrogen receptor

ETS:

Erythroblast Transformation Specific

GLI:

Glioma-associated oncogene

Her-2:

Human epidermal growth factor receptor-2

HIF-1:

Hypoxia-inducible factor

IL-6:

Interleukin-6

IFN-γ:

Interferon gamma

JAK:

Janus kinase

mTOR:

Mammalian target of rapamycin

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

PIM1:

Proviral integration site for Moloney murine leukemia virus-1

PR:

Progesterone receptor

SOCS 1:

Suppressor of cytokine signaling proteins 1

SOCS 3:

Suppressor of cytokine signaling proteins 3

SRC-1:

Steroid receptor coactivator-1

STAT3:

Signal transducer and activator of transcription 3

TNBC:

Triple-Negative Breast Cancer

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Funding

The authors would like to thank the Department of Health Research (DHR), Govt of India; New Delhi for funding SM under a DHR-Women Scientist Scheme (R.12013/07/2017-HR).

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Authors and Affiliations

  1. Department of Pathology and Cancer Screening, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata, 700026, India

    Sutapa Mahata, Pranab K. Sahoo, Ranita Pal, Sinjini Sarkar, Tanuma Mistry, Sushmita Ghosh & Vilas D. Nasare

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  1. Sutapa Mahata
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  2. Pranab K. Sahoo
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  3. Ranita Pal
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  4. Sinjini Sarkar
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  6. Sushmita Ghosh
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  7. Vilas D. Nasare
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Correspondence to Vilas D. Nasare.

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Mahata, S., Sahoo, P.K., Pal, R. et al. PIM1/STAT3 axis: a potential co-targeted therapeutic approach in triple-negative breast cancer. Med Oncol 39, 74 (2022). https://doi.org/10.1007/s12032-022-01675-2

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