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Advances in Targeted Therapy and Biomarker Research for Endocrine-Related Cancers

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Editorial11 December 2024
Editorial: Advances in targeted therapy and biomarker research for endocrine-related cancers

The field of endocrine-related cancers is undergoing rapid transformation, fueled by significant strides in deciphering the molecular and genetic foundations of these diseases (1). These cancers, which encompass a range of malignancies affecting the endocrine system, present unique challenges due to their intricate interactions with hormonal signaling pathways (2). In recent years, the surge in the development of targeted therapies has sparked optimism for more precise and personalized treatment options (3). Simultaneously, the identification and validation of biomarkers have become crucial for improving diagnosis, prognosis, and treatment decision-making, marking a significant shift toward precision medicine. Moreover, cutting-edge research techniques, including organoid cultures and organ-on-a-chip systems, have emerged, providing more accurate and reliable models for studying tumor biology and drug responses (4). These innovations highlight the growing importance of translational medicine, which bridges the gap between laboratory findings and clinical applications, opening new pathways for understanding and addressing endocrine-related cancers. This dynamic landscape calls for a comprehensive examination of both current trends and future directions in the research and treatment of these complex diseases.The aim of this Research Topic was to accelerate pioneering research and deepen our understanding of endocrine-related cancers. By spotlighting groundbreaking studies on targeted therapies, biomarker discovery, and advanced modeling approaches like organoids and organ-on-a-chip platforms, we seek to foster a connection between experimental research and clinical practice. Our goal was to establish a collaborative forum that not only disseminates cutting-edge scientific insights but also stimulates the development of innovative therapeutic strategies, ultimately enhancing patient outcomes in the field of endocrine oncology. A series of articles have been published under this Research Topic, as shown below.Head and neck paragangliomas (HNPGNs) are infrequent tumors that originate from the parasympathetic paraganglia located at the skull base and neck (5). Standard treatment options, including surgery and radiotherapy, carry considerable risks due to the tumors' close proximity to critical blood vessels and cranial nerves (6). Diagnosing HNPGNs is particularly challenging, as distinguishing between benign and malignant forms cannot be solely achieved through histology or imaging (7). Gaining a deeper understanding of the tumor microenvironment in HNPGNs could unveil key markers associated with tumor growth and malignancy, potentially enabling earlier detection, more effective targeted therapies, and strategies to prevent recurrences and metastasis. Thyroid cancer originates in the thyroid gland, a butterfly-shaped organ located at the base of the neck, and its incidence has been rising in recent years (10). Key risk factors include radiation exposure, genetic mutations, and family history, with women being more frequently affected (11). Treatment options are largely determined by the cancer's type and stage, with surgery to remove the thyroid being a common approach.Remaining cancer cells are often treated with radioactive iodine therapy (12). Given the complexity of the disease and the need for personalized care, targeted therapies and biomarker research have become crucial areas of focus in thyroid cancer management.

of biomarker research, and the latest advancements in targeted therapy for thyroid cancer. They identified several critical molecular markers, including BRAF mutations, RAS mutations, RET/PTC rearrangements, PAX8/PPARγ rearrangements, and TERT promoter mutations, which are strongly associated with the disease. Understanding these biomarkers enables more precise diagnosis, prognostication, and tailored treatment plans for patients. Targeted treatments for thyroid cancer aim to disrupt the cancer cells' growth mechanisms by targeting specific molecules involved in tumor development. Among the key approaches identified are tyrosine kinase inhibitors, thyroid hormone receptor antagonists, radioactive iodine therapy, immunotherapy, and gene-targeted therapies. Further investigation is focused on discovering new therapeutic targets, improving treatment tolerance, and developing combination therapies. The evolving scientific landscape provides hope for more effective, personalized treatment options for thyroid cancer.Liver hepatocellular carcinoma (LIHC) is the most prevalent primary liver cancer and the third leading cause of cancer-related deaths worldwide (13). It affects individuals with chronic liver diseases, such as those caused by viral hepatitis, alcoholrelated liver damage, or non-alcoholic fatty liver disease (14). Identifying clinical and biochemical factors that can pinpoint high-risk groups is crucial for timely intervention through imaging or screening. Improving prevention efforts and developing novel therapies are essential for better outcomes. Yu et al. evaluated the causal impact of exposure factors, including Alzheimer's disease, platelet count, ambidextrousness, cigarettes smoked per day, alcohol consumption, and endocarditis, on the risk of LIHC using a two-sample MR study. Their findings provided compelling evidence supporting a causal relationship between reduced platelet levels and heightened vulnerability to LIHC in the European population. Therefore, it is recommended to prioritize the management of individuals with lower platelet counts to minimize their risk of developing LIHC. As a result, this study contributes to an expanding body of literature indicating that targeting platelet-related agents holds promise as a potential therapeutic approach for early detection and treatment of LIHC.In summary, the articles collected under this Research Topic provide a comprehensive examination of targeted therapies and biomarkers for endocrine-related cancers. By focusing on the molecular and genetic underpinnings of these tumors, the studies presented offer critical insights into improving diagnosis, prognosis, and treatment personalization. The identification and validation of specific biomarkers have the potential to enhance early detection and guide more precise, individualized treatment approaches. The development of targeted therapies, aimed at disrupting key signaling pathways involved in tumor growth, represents a promising avenue for improving patient outcomes. These findings contribute to shaping the future direction of clinical management for endocrine-related cancers. Lastly, we thank all our contributors who enriched this Research Topic by submitting manuscripts highlighting their highly valuable and interesting research studies.

1,824 views

4 citations

Mechanisms of endocrine resistance in hormone receptor-positive breast cancer
REVIEW
31 October 2024
Mechanisms of endocrine resistance in hormone receptor-positive breast cancer
Yuan Gao, 3 more and Lihua Kang
Hormone receptor-positive breast cancer may recur or metastasize years or decades after its diagnosis. Furthermore, hormone receptor expression may persist in relapsed or metastatic cancer cells. Endocrine therapy is one of the most efficacious treatments for hormone receptor-positive breast cancers. Nevertheless, a considerable proportion of patients develop resistance to endocrine therapy. Previous studies have identified numerous mechanisms underlying drug resistance, such as epigenetic abnormalities in the estrogen receptor (ER) genome, activation of ER-independent ligands, and alterations in signaling pathways including PI3K/AKT/mTOR, Notch, NF-κB, FGFR, and IRE1-XBP1. This article reviews the mechanisms of endocrine resistance in hormone receptor-positive advanced breast cancer, drawing from previous studies, and discusses the latest research advancements and prospects.

11,304 views

38 citations

ORIGINAL RESEARCH
15 November 2024
Functional analysis of fibroblasts and macrophages in head and neck paragangliomas
Paramita Baruah, 12 more and Christopher D. Buckley

3,457 views

Identifying new biomarkers and potential therapeutic targets for breast cancer through the integration of human plasma proteomics: a Mendelian randomization study and colocalization analysis
The proteome is a crucial reservoir of targets for cancer treatment.While some targeted therapies have been developed, there are still significant challenges in early diagnosis and treatment, highlighting the need to identify new biomarkers and therapeutic targets for breast cancer. Therefore, we conducted a comprehensive proteome-wide Mendelian randomization (MR) study to identify novel biomarkers and potential therapeutic targets for breast cancer.Methods: Protein quantitative trait locus (pQTL) data were extracted from two published plasma proteome-wide association studies. Genetic variants associated with breast cancer were obtained from the Breast Cancer Association Consortium, which included 133,384 cases and 113,789 controls, and the Finnish cohort study, comprising 18,786 cases and 182,927 controls. We employed summary-based MR and colocalization methods to identify potential drug targets for breast cancer, which were subsequently validated using a two-sample MR approach. Finally, a protein-protein interaction (PPI) network was constructed to detect interactions between the identified proteins and existing cancer drug targets.Results: Gene-predicted levels of ten proteins were associated with breast cancer risk.Decreased levels of CASP8, DDX58, CPNE1, ULK3, PARK7, and BTN2A1, as well as increased levels of TNFRSF9, TNXB, DNPH1, and TLR1, were linked to an elevated risk of breast cancer. Among these, CASP8 and DDX58 were supported by tier-one evidence, while CPNE1, ULK3, PARK7, and TNFRSF9 received tier-two evidence support. The remaining proteins, TNXB, BTN2A1, DNPH1, and TLR1, were supported by tier-three evidence. CASP8, DDX58, CPNE1, ULK3, PARK7, and TNFRSF9 have already been identified as targets in drug development and potential therapeutic targets for breast cancer treatment. Additionally, ULK3 showed promise as a prognostic biomarker for breast cancer.The present study identified several novel potential drug targets and biomarkers for breast cancer, providing new insights into its diagnosis and treatment.The integration of PPI and druggability evaluations enhances the prioritization of these therapeutic targets, paving the way for future drug development efforts.

5,913 views

16 citations

MINI REVIEW
8 October 2024
Unveiling new chapters in medullary thyroid carcinoma therapy: advances in molecular genetics and targeted treatment strategies
Jia-Xuan Huai, 6 more and Xi-Qiao Zhou

5,170 views

5 citations

ORIGINAL RESEARCH
7 August 2024
A nomogram based on inflammation and nutritional biomarkers for predicting the survival of breast cancer patients
Caibiao Wei, 7 more and Miaofeng Liu

3,565 views

13 citations

SYSTEMATIC REVIEW
29 August 2024
The prognostic value of preoperative plasma fibrinogen in Asian patients with urothelial cancer: a systematic review and meta-analysis
Zhengqing Bao, 4 more and Jianwei Wang

1,789 views

4 citations

ORIGINAL RESEARCH
10 July 2024
Exploring the multifaceted antitumor activity of axitinib in lung carcinoids
Monica Oldani, 9 more and Giovanni Vitale

2,570 views

2 citations

ORIGINAL RESEARCH
18 June 2024
Is the percentage of hormone receptor positivity in HR+ HER2-metastatic breast cancer patients receiving CDK 4/6 inhibitor with endocrine therapy predictive and prognostic?
Merve Keskinkilic, 2 more and Ilhan Oztop

3,673 views

5 citations

METHODS
31 May 2024
Cathepsins and cancer risk: a Mendelian randomization study
Tingting Deng, 7 more and Fanjie Liu

6,873 views

16 citations

ORIGINAL RESEARCH
22 May 2024
Causal associations between platelet count, alcohol consumption, and the risk of liver hepatocellular carcinoma based on a Mendelian randomization study
Lihua Yu, 4 more and Hao Hu

3,602 views

4 citations

Advances in targeted therapy and biomarker research in thyroid cancer
REVIEW
4 March 2024
Advances in targeted therapy and biomarker research in thyroid cancer
Mei Guo, 3 more and Chun Zhang

9,382 views

39 citations