Targeting STATs for Anti-cancer Therapy

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (28 February 2023) | Viewed by 8598

Special Issue Editor


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Guest Editor
UPMC Hillman Cancer Center, Pittsburgh, PA, USA
Interests: STAT3; biomarkers; signal transduction; cancer therapeutics; chemoprevention; cancer epigenetics; lung cancer; early detection

Special Issue Information

Dear Colleagues,

We are extremely pleased to offer a special issue focused on Targeting STATs for Anti-cancer Therapy, for the journal Cancer. We invite you to share your breakthrough research on STAT pathway with the scientific community by publishing in this special issue.

Aim - Publish novel therapeutic strategies as suitable and effective STAT inhibitors for clinical application in cancer patients. 

Scope - Publish high quality research articles targeting STAT signaling in the tumor and tumor microenvironment using innovative or incremental therapeutic approaches. Signal Transducers and Activators of Transcription (STATs) family members, particularly STAT3 and STAT5 are constitutively activated in many cancers and are thought to be ideal candidates for anti-cancer therapy. Several strategies have been explored to target the two oncogenes. Although some inhibitors showed profound antitumor activity in inhibiting the biological function of the oncogenes, however there are no clinical grade lead inhibitors. The key challenge is to discover high-quality selective inhibitors with profound antitumor activity.

In this Special Issue, original research articles and reviews are welcome. Research articles may include (but are not limited) to the following:

  • Drug development targeting the STAT pathway
  • Therapeutic inhibition of the STAT pathway in preclinical cancer models
  • Identifying mechanism of action contributing to hyperactivation of the STAT molecules
  • Clinical grade STAT inhibitors in clinical trials
  • Combinationtreatment strategies with immune checkpoint inhibitors 
  • Identify dysregulation of key molecules influencing STAT molecule activation for efficient patient stratification to benefit from therapy

We look forward to receiving your contributions.

Dr. Malabika Sen
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cancer
  • tumor
  • tumor microenvironment
  • STAT3 and STAT5 inhibitors
  • mechanism of action
  • drug development
  • negative regulators
  • mutation
  • methylation
  • immunotherapy

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Published Papers (3 papers)

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Review

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30 pages, 1847 KiB  
Review
Exploring Novel Frontiers: Leveraging STAT3 Signaling for Advanced Cancer Therapeutics
by Taiwo Adesoye, Debasish Tripathy, Kelly K. Hunt and Khandan Keyomarsi
Cancers 2024, 16(3), 492; https://doi.org/10.3390/cancers16030492 - 24 Jan 2024
Cited by 5 | Viewed by 3102
Abstract
Signal Transducer and Activator of Transcription 3 (STAT3) plays a significant role in diverse physiologic processes, including cell proliferation, differentiation, angiogenesis, and survival. STAT3 activation via phosphorylation of tyrosine and serine residues is a complex and tightly regulated process initiated by upstream signaling [...] Read more.
Signal Transducer and Activator of Transcription 3 (STAT3) plays a significant role in diverse physiologic processes, including cell proliferation, differentiation, angiogenesis, and survival. STAT3 activation via phosphorylation of tyrosine and serine residues is a complex and tightly regulated process initiated by upstream signaling pathways with ligand binding to receptor and non-receptor-linked kinases. Through downstream deregulation of target genes, aberrations in STAT3 activation are implicated in tumorigenesis, metastasis, and recurrence in multiple cancers. While there have been extensive efforts to develop direct and indirect STAT3 inhibitors using novel drugs as a therapeutic strategy, direct clinical application remains in evolution. In this review, we outline the mechanisms of STAT3 activation, the resulting downstream effects in physiologic and malignant settings, and therapeutic strategies for targeting STAT3. We also summarize the pre-clinical and clinical evidence of novel drug therapies targeting STAT3 and discuss the challenges of establishing their therapeutic efficacy in the current clinical landscape. Full article
(This article belongs to the Special Issue Targeting STATs for Anti-cancer Therapy)
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31 pages, 1865 KiB  
Review
The Role of STATs in Ovarian Cancer: Exploring Their Potential for Therapy
by David Standing, Emma Feess, Satvik Kodiyalam, Michael Kuehn, Zachary Hamel, Jaimie Johnson, Sufi Mary Thomas and Shrikant Anant
Cancers 2023, 15(9), 2485; https://doi.org/10.3390/cancers15092485 - 26 Apr 2023
Cited by 6 | Viewed by 2908
Abstract
Ovarian cancer (OvCa) is a deadly gynecologic malignancy that presents many clinical challenges due to late-stage diagnoses and the development of acquired resistance to standard-of-care treatment protocols. There is an increasing body of evidence suggesting that STATs may play a critical role in [...] Read more.
Ovarian cancer (OvCa) is a deadly gynecologic malignancy that presents many clinical challenges due to late-stage diagnoses and the development of acquired resistance to standard-of-care treatment protocols. There is an increasing body of evidence suggesting that STATs may play a critical role in OvCa progression, resistance, and disease recurrence, and thus we sought to compile a comprehensive review to summarize the current state of knowledge on the topic. We have examined peer reviewed literature to delineate the role of STATs in both cancer cells and cells within the tumor microenvironment. In addition to summarizing the current knowledge of STAT biology in OvCa, we have also examined the capacity of small molecule inhibitor development to target specific STATs and progress toward clinical applications. From our research, the best studied and targeted factors are STAT3 and STAT5, which has resulted in the development of several inhibitors that are under current evaluation in clinical trials. There remain gaps in understanding the role of STAT1, STAT2, STAT4, and STAT6, due to limited reports in the current literature; as such, further studies to establish their implications in OvCa are necessitated. Moreover, due to the deficiency in our understanding of these STATs, selective inhibitors also remain elusive, and therefore present opportunities for discovery. Full article
(This article belongs to the Special Issue Targeting STATs for Anti-cancer Therapy)
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Other

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10 pages, 275 KiB  
Commentary
Combining STAT3-Targeting Agents with Immune Checkpoint Inhibitors in NSCLC
by Kostas A. Papavassiliou, Georgios Marinos and Athanasios G. Papavassiliou
Cancers 2023, 15(2), 386; https://doi.org/10.3390/cancers15020386 - 6 Jan 2023
Cited by 11 | Viewed by 2017
Abstract
Despite recent therapeutic advances, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor (TF) with multiple tumor-promoting effects in NSCLC, including proliferation, anti-apoptosis, angiogenesis, invasion, metastasis, immunosuppression, and [...] Read more.
Despite recent therapeutic advances, non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related death. Signal transducer and activator of transcription 3 (STAT3) is a transcription factor (TF) with multiple tumor-promoting effects in NSCLC, including proliferation, anti-apoptosis, angiogenesis, invasion, metastasis, immunosuppression, and drug resistance. Recent studies suggest that STAT3 activation contributes to resistance to immune checkpoint inhibitors. Thus, STAT3 represents an attractive target whose pharmacological modulation in NSCLC may assist in enhancing the efficacy of or overcoming resistance to immune checkpoint inhibitors. In this review, we discuss the biological mechanisms through which STAT3 inhibition synergizes with or overcomes resistance to immune checkpoint inhibitors and highlight the therapeutic strategy of using drugs that target STAT3 as potential combination partners for immune checkpoint inhibitors in the management of NSCLC patients. Full article
(This article belongs to the Special Issue Targeting STATs for Anti-cancer Therapy)
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