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Involvement of the kynurenine pathway in breast cancer: updates on clinical research and trials.

ABSTRACT: Breast cancer (BrCa) is the leading cause of cancer incidence and mortality in women worldwide. While BrCa treatment has been shown to be highly successful if detected at an early stage, there are few effective strategies to treat metastatic tumours. Hence, metastasis remains the main cause in most of BrCa deaths, highlighting the need for new approaches in this group of patients. Immunotherapy has been gaining attention as a new treatment for BrCa metastasis and the kynurenine pathway (KP) has been suggested as one of the potential targets. The KP is the major biochemical pathway in tryptophan (TRP) metabolism, catabolising TRP to nicotinamide adenine dinucleotide (NAD⁺). The KP has been reported to be elevated under inflammatory conditions such as cancers and that its activity suppresses immune surveillance. Dysregulation of the KP has previously been reported implicated in BrCa. This review aims to discuss and provide an update on the current mechanisms involved in KP-mediated immune suppression and cancer growth. Furthermore, we also provide a summary on 58 studies about the involvement of the KP and BrCa and five clinical trials targeting KP enzymes and their outcome.

SUBMITTER: Girithar HN

PROVIDER: S-EPMC10338682 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Involvement of the kynurenine pathway in breast cancer: updates on clinical research and trials.

Girithar Hemaasri-Neya HN Staats Pires Ananda A Ahn Seong Beom SB Guillemin Gilles J GJ Gluch Laurence L Heng Benjamin B

British journal of cancer 20230411 2

Breast cancer (BrCa) is the leading cause of cancer incidence and mortality in women worldwide. While BrCa treatment has been shown to be highly successful if detected at an early stage, there are few effective strategies to treat metastatic tumours. Hence, metastasis remains the main cause in most of BrCa deaths, highlighting the need for new approaches in this group of patients. Immunotherapy has been gaining attention as a new treatment for BrCa metastasis and the kynurenine pathway (KP) has ...[more]

PMID: 37041200

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Project description:In recent decades, the increasing interest in the field of immunotherapy has fostered an intense investigation of the breast cancer (BC) immune microenvironment. In this context, tumor-infiltrating lymphocytes (TILs) have emerged as a clinically relevant and highly reproducible biomarker capable of affecting BC prognosis and response to treatment. Indeed, the evaluation of TILs on primary tumors proved to be strongly prognostic in triple-negative (TN) BC patients treated with either adjuvant or neoadjuvant chemotherapy, as well as in early TNBC patients not receiving any systemic treatment, thus gaining level-1b evidence in this setting. In addition, a strong relationship between TILs and pathologic complete response after neoadjuvant chemotherapy has been reported in all BC subtypes and the prognostic role of higher TILs in early HER2-positive breast cancer patients has also been demonstrated. The interest in BC immune infiltrates has been further fueled by the introduction of the first immune checkpoint inhibitors in the treatment armamentarium of advanced TNBC in patients with PD-L1-positive status by FDA-approved assays. However, despite these advances, a biomarker capable of reliably and exhaustively predicting immunotherapy benefit in BC is still lacking, highlighting the imperative need to further deepen this issue. Finally, more comprehensive evaluation of immune infiltrates integrating both the quantity and quality of tumor-infiltrating immune cells and incorporation of TILs in composite scores encompassing other clinically or biologically relevant biomarkers, as well as the adoption of software-based and/or machine learning platforms for a more comprehensive characterization of BC immune infiltrates, are emerging as promising strategies potentially capable of optimizing patient selection and stratification in the research field. In the present review, we summarize available evidence and recent updates on immune infiltrates in BC, focusing on current clinical applications, potential clinical implications and major unresolved issues.

Project description:BackgroundBreast cancer, particularly triple-negative (TNBC), is a leading malignancy with aggressive traits and high metastasis rates. Clinical trial is an important tool for optimizing therapeutic strategies in the evaluation of the safety and efficacy for TNBC. Our bibliometric study of TNBC clinical trials aims to assess therapeutic strategies, identify trends, and explore advancements in treatment. We focus on mapping knowledge development, including key research entities and topics, and analyzing research trends and emerging methods. This analysis intends to inform future research, especially in personalized and precision medicine for TNBC.MethodsWe selected publications on clinical trials for the treatment of TNBC from 1997 to 2024 in the Web of Science Core Collection (WoSCC). After an initial screening, we downloaded key data including titles, publication years, authors, countries, institutional affiliations, journals, keywords, and abstracts, and saved them in BibTex format. We then conducted a bibliometric analysis using Bibliometrix in R and VOSviewer to illustrate the prospects, highlights, and trends of TNBC treatment options. Furthermore, to emphasize the hot topics in TNBC treatment strategies, we performed a bibliometric analysis of immunotherapy using the same approach.Results1907 publications were included, most of which were from China, Italy, and the United States. The number of annual publications has increased dramatically since 2010. The focus of TNBC clinical trial research has shifted from understanding the biology, such as breast cancer subtyping and genotyping, to novel therapeutic approaches. The major advancement in clinical trials is the switch from late-stage palliative treatment to early preoperative neoadjuvant therapy, as more TNBC cases are discovered at an early stage. Immunotherapy is also highlighted with additional alternatives for advanced or metastasized TNBC, such as targeted inhibitors with unusual mutation rates and antibody drug conjugates (ADC).ConclusionsThis investigation made it apparent how immunotherapy has recently made major advancements in TNBC treatment plans and how ADCs, or targeted therapies, are currently popular for TNBC. By identifying significant papers, comprehending trending topics, and collaborating across multiple disciplines, this study may accelerate research on TNBC therapy options.

Dataset Information

Involvement of the kynurenine pathway in breast cancer: updates on clinical research and trials.

Publications

Involvement of the kynurenine pathway in breast cancer: updates on clinical research and trials.

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