The potential and controversy of targeting STAT family members in cancer

Seminars in Cancer Biology, Journal Year: 2019, Volume and Issue: 60, P. 41 - 56

Published: Oct. 9, 2019

The Signal Transducer and Activator of Transcription (STAT) family proteins consists transcription factors that play a complex essential role in the regulation physiologic cell processes, such as proliferation, differentiation, apoptosis angiogenesis, serves to organize epigenetic landscape immune cells. To date, seven STAT genes have been identified human genome; STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b STAT6. They all account for diverse effects response extracellular signaling proteins, mainly by altering gene effector Members implicated cancer development, progression, metastasis, survival resistance treatment. Particularly STAT3 STAT5 are interest biology. currently considered oncogenes, but their is embedded into delicate balance between different (counteracting) factors, thus, some contexts they can tumor suppressive role. Assessing mutations well screening aberrant pathway activation may predict sensitivity immunotherapy targeted inhibition. In present comprehensive review literature, we discuss in-depth each member cancer, assemble cutting-edge information on use these molecules potential biomarkers targets treatment, address why clinical implementation controversy.

Language: Английский

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Doxorubicin—An Agent with Multiple Mechanisms of Anticancer Activity

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 659 - 659

Published: Feb. 19, 2023

Doxorubicin (DOX) constitutes the major constituent of anti-cancer treatment regimens currently in clinical use. However, precise mechanisms DOX’s action are not fully understood. Emerging evidence points to pleiotropic anticancer activity DOX, including its contribution DNA damage, reactive oxygen species (ROS) production, apoptosis, senescence, autophagy, ferroptosis, and pyroptosis induction, as well immunomodulatory role. This review aims collect information on DOX influence anti-tumor immune response, providing a rationale behind importance modern cancer therapy.

Language: Английский

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Paradigms on Immunotherapy Combinations with Chemotherapy

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(6), P. 1353 - 1367

Published: March 12, 2021

Abstract Checkpoint inhibitors are being added to standard-of-care chemotherapy in multiple clinical trials. Success has been reported non–small and small cell lung carcinomas urothelial, head neck, gastric, esophageal cancers, promising results already available triple-negative breast pancreatic malignancies. The potential mechanisms of synergy include immunogenic tumor death, antiangiogenesis, selective depletion myeloid immunosuppressive cells, lymphopenia, which reduces regulatory T cells makes room for proliferation effector cells. However, regimens have not optimized such combinations, perhaps explaining some recent trial disappointments. Approaches make the most chemoimmunotherapy neoadjuvant adjuvant schemes. Significance: Immunotherapy cancer based on PD-1/PD-L1 blockade prompted a revolution management. Evidence phase III trials supports combinations immunotherapy with number malignant diseases. This review focuses evidence provides an overview synergistic action opportunities optimize regimens.

Language: Английский

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The role of PD-1/PD-L1 and application of immune-checkpoint inhibitors in human cancers

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 13, 2022

Programmed cell death protein-1 (PD-1) is a checkpoint receptor expressed on the surface of various immune cells. PD-L1, natural for PD-1, mainly in tumor Studies have indicated that PD-1 and PD-L1 are closely associated with progression human cancers promising biomarkers cancer therapy. Moreover, interaction one important mechanism by which tumors generate escape. This article provides review role PD-L1/PD-1, mechanisms response resistance, as well immune-related adverse events treatment anti-PD-1/PD-L1 immunotherapy cancers. we summarized large number clinical trials to successfully reveal PD-1/PD-L1 Immune-checkpoint inhibitors manifested therapeutic effects, been evaluated from different perspectives, including overall survival, objective effective rate medium progression-free survival. Finally, pointed out current problems faced its future prospects. Although widely used cancers, tough challenges still remain. Combination therapy predictive models based integrated biomarker determination theory may be directions application treating

Language: Английский

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Molecular Mechanisms of Radiation-Induced Cancer Cell Death: A Primer

Frontiers in Cell and Developmental Biology, Journal Year: 2020, Volume and Issue: 8

Published: Feb. 13, 2020

Radiation therapy (RT) is responsible for at least 40% of cancer cures, however treatment resistance remains a clinical problem. There have been recent advances in understanding the molecular mechanisms radiation-induced cell death. The type death after radiation depends on number factors including type, dose and quality, oxygen tension, TP53 status, DNA repair capacity, cycle phase time exposure, microenvironment. Mitotic catastrophe (a pathway preceding that happens mitosis or as consequence aberrant mitotic progression) primary context solid cancers, although small subset cancers such haematopoietic malignancies, results immediate interphase apoptosis, occurring within hours exposure. intense therapeutic interest using stereotactic ablative body radiotherapy (SABR), precise, high-dose form RT given fractions, to prime immune system killing, but optimal fractionation remain unclear. Additionally, promising novel radiosensitisers targeting pathways are being trialled. In increasing use SABR agents clinic, we provide an updated primer major types death, focussing their mechanisms, affecting initiation, implications immunogenicity.

Language: Английский

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Tumor immunotherapies by immune checkpoint inhibitors (ICIs); the pros and cons

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: April 7, 2022

Abstract The main breakthrough in tumor immunotherapy was the discovery of immune checkpoint (IC) proteins, which act as a potent suppressor system by myriad mechanisms. After that, scientists focused on molecules mainly. Thereby, much effort spent to progress novel strategies for suppressing these inhibitory axes, resulting evolution inhibitors (ICIs). Then, ICIs have become promising approach and shaped paradigm shift immunotherapies. CTLA-4 plays an influential role attenuation induction naïve memory T cells engagement with its responding ligands like B7-1 (CD80) B7-2 (CD86). Besides, PD-1 is predominantly implicated adjusting cell function peripheral tissues through interaction programmed death-ligand 1 (PD-L1) PD-L2. Given their suppressive effects anti-tumor immunity, it has firmly been documented that based therapies can be practical rational therapeutic approaches treat cancer patients. Nonetheless, inherent or acquired resistance ICI some treatment-related toxicities restrict application clinic. current review will deliver comprehensive overview human tumors alone combination other modalities support more desired outcomes lower

Language: Английский

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New insights into the activities and toxicities of the old anticancer drug doxorubicin

FEBS Journal, Journal Year: 2020, Volume and Issue: 288(21), P. 6095 - 6111

Published: Oct. 6, 2020

The anthracycline drug doxorubicin is among the most used—and useful—chemotherapeutics. While highly effective in treatment of various hematopoietic malignancies and solid tumours, its application limited by severe adverse effects, including irreversible cardiotoxicity, therapy‐related gonadotoxicity. This continues to motivate investigation into mechanisms activities toxicities, with aim overcome latter without sacrificing former. It has long been appreciated that causes DNA double‐strand breaks due poisoning topoisomerase II. More recently, it became clear also leads chromatin damage achieved through eviction histones from select sites genome. Evaluation these analogues revealed makes a major contribution efficacy drugs. Furthermore, DNA‐damaging effect conspires cause number effects. Structure–activity relationships within family offer opportunities for chemical separation towards development In this review, we elaborate on our current understanding different their contributions side We then perspective how old anticancer can be amended new ways benefit cancer patients, providing improved quality life.

Language: Английский

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Advancements in clinical aspects of targeted therapy and immunotherapy in breast cancer

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: July 6, 2023

Abstract Breast cancer is the second leading cause of death for women worldwide. The heterogeneity this disease presents a big challenge in its therapeutic management. However, recent advances molecular biology and immunology enable to develop highly targeted therapies many forms breast cancer. primary objective therapy inhibit specific target/molecule that supports tumor progression. Ak strain transforming, cyclin-dependent kinases, poly (ADP-ribose) polymerase, different growth factors have emerged as potential targets subtypes. Many drugs are currently undergoing clinical trials, some already received FDA approval monotherapy or combination with other treatment yet achieve promise against triple-negative (TNBC). In aspect, immune has come up promising approach specifically TNBC patients. Different immunotherapeutic modalities including immune-checkpoint blockade, vaccination, adoptive cell transfer been extensively studied setting cancer, especially approved blockers chemotherapeutic treat several trials ongoing. This review provides an overview developments advancements immunotherapies treatment. successes, challenges, prospects were critically discussed portray their profound prospects.

Language: Английский

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Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies

npj Breast Cancer, Journal Year: 2020, Volume and Issue: 6(1)

Published: Oct. 16, 2020

Triple-negative breast cancer (TNBC) is not a unique disease, encompassing multiple entities with marked histopathological, transcriptomic and genomic heterogeneity. Despite several efforts, classifications have remained merely theoretic most of the patients are being treated chemotherapy. Driver alterations in potentially targetable genes, including PIK3CA AKT, been identified across TNBC subtypes, prompting implementation biomarker-driven therapeutic approaches. However, biomarker-based treatments as well immune checkpoint inhibitor-based immunotherapy provided contrasting limited results so far. Accordingly, better characterization contexture underpinning TNBC, translation lessons learnt metastatic disease to early setting would improve patients' outcomes. The application multi-omics technologies, biocomputational algorithms, assays for minimal residual monitoring novel clinical trial designs strongly warranted pave way toward personalized anticancer treatment TNBC.

Language: Английский

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Rational combinations of targeted cancer therapies: background, advances and challenges

Nature Reviews Drug Discovery, Journal Year: 2022, Volume and Issue: 22(3), P. 213 - 234

Published: Dec. 12, 2022

Language: Английский

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