Review
Oncology
Dan Yan, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: MERTK and AXL are abnormally expressed in the majority of NSCLCs, providing a survival advantage for cells and correlating with metastasis, drug resistance, and disease progression. Host tumor infiltrating cells' TAM receptors also play crucial roles in the immunosuppressive tumor microenvironment. These factors make MERTK and AXL attractive targets for NSCLC treatment.
Article
Multidisciplinary Sciences
Marta Nyakas, Karianne Giller Fleten, Mads Haugland Haugen, Nikolai Engedal, Christina Sveen, Inger Nina Farstad, Vivi Ann Florenes, Lina Prasmickaite, Gunhild Mari Maelandsmo, Kotryna Seip
Summary: This study investigated the therapeutic potential of combining an AXL inhibitor (AXLi) and a clinically relevant BRAF inhibitor (BRAFi) for the treatment of metastatic melanoma. The results showed that AXL was expressed in the majority of melanoma lymph node metastases. In vitro experiments demonstrated that the combination of AXLi and BRAFi resulted in the largest reduction in cell viability. Moreover, pre-clinical studies using AXL(high) melanoma models showed a therapeutic benefit of adding AXLi to the BRAF-targeted therapy. Mechanistic insights revealed that AXLi potentiated BRAFi-induced apoptosis, stimulated ferroptosis, and inhibited autophagy. Overall, this study suggests that combining AXLi with standard therapy could improve the therapeutic outcome in metastatic melanoma.
SCIENTIFIC REPORTS
(2022)
Review
Biochemistry & Molecular Biology
Mai Tanaka, Dietmar W. Siemann
Summary: Dysregulated signaling pathways in cancer cells and the tumor microenvironment, including the Axl and Gas6 pathways, have led to the development of therapeutic agents targeting the Gas6/Axl pathway. Promising results have been observed in both preclinical and clinical settings, indicating potential clinical efficacy of targeting Gas6 and Axl.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Dan Yan, Justus M. Huelse, Dmitri Kireev, Zikang Tan, Luxiao Chen, Subir Goyal, Xiaodong Wang, Stephen Frye, Madhusmita Behera, Frank Schneider, Suresh S. Ramalingam, Taofeek Owonikoko, H. Shelton Earp, Deborah DeRyckere, Douglas K. Graham
Summary: Acquired resistance is inevitable in non-small cell lung cancers (NSCLCs) treated with osimertinib (OSI). Activation of MERTK is associated with OSI resistance and inhibition of MERTK kinase can resensitize resistant cells to OSI.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Oncology
Prachi Mishra, Dipranjan Laha, Robert Grant, Naris Nilubol
Summary: This article reviews current treatment practices for thyroid cancer and emphasizes on novel targeted molecular therapy. With rapidly expanding knowledge of the molecular biology and increased availability of genetic testing, exciting paradigm shifts in treatment strategies have been observed. Targeted therapies and personalized treatments have become a trend with the development of new treatment strategies, accelerating the advancement of treatments for thyroid cancer.
Review
Chemistry, Medicinal
Adileh Ayati, Setareh Moghimi, Mahsa Toolabi, Alireza Foroumadi
Summary: Despite advancements in cancer treatment, EGFR inhibitors have shown significant improvement in targeted therapy. However, the emergence of epigenetic mutation and resistance issues have limited their effectiveness, leading to the need for further research in this field. Recent studies have focused on genetic alterations in the EGFR tyrosine kinase domain, resulting in the development of more selective and effective inhibitors.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Pharmacology & Pharmacy
Gian Marco Leone, Saverio Candido, Alessandro Lavoro, Silvia Vivarelli, Giuseppe Gattuso, Daniela Calina, Massimo Libra, Luca Falzone
Summary: Lung cancer is the second most diagnosed tumor with the highest mortality rate. Recent progress in the treatment of lung cancer includes targeted therapies and immunotherapy, which have been approved in clinical practice. This review discusses the current and ongoing clinical studies on targeted therapies and immune-checkpoint inhibitors for lung cancer, as well as the advantages and limitations of these new therapeutic approaches. Furthermore, the importance of human microbiota as biomarkers and therapeutic targets for lung cancer is analyzed. The future research milestones in personalized treatment for lung cancer are expected to consider the genetic landscape, immune background, and individual variables such as patient-specific gut microbial composition.
Review
Biochemistry & Molecular Biology
Marco de Scordilli, Anna Michelotti, Elisa Bertoli, Elisa De Carlo, Alessandro Del Conte, Alessandra Bearz
Summary: The scenario of neoadjuvant and adjuvant settings in non-small cell lung cancer (NSCLC) is rapidly evolving. Molecular analysis and PD-L1 evaluation have become routine assessments. New treatment options have been approved, including osimertinib for EGFRm patients and ICIs in both adjuvant and neoadjuvant settings. However, mature data on overall survival benefits are not yet available.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Ningning Yan, Sanxing Guo, Huixian Zhang, Ziheng Zhang, Shujing Shen, Xingya Li
Summary: This review summarizes the characteristics and challenges of BRAF mutations in NSCLC, as well as the treatment strategies and resistance mechanisms of BRAF-targeted therapy.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Keunchil Park, Gee-Chen Chang, Giuseppe Curigliano, Wan-Teck Lim, Ross A. Soo, Miguel A. Molina-Vila, Valerie Cattan, Helene Darville, Eric Gandossi, Veronika Smutna, Isabelle Sudey, Santiago Viteri
Summary: The combination of gefitinib with S49076 showed limited anti-tumour activity with good tolerability in EGFR TKI-resistant NSCLC patients. The study did not reveal a clear trend in activity within specific molecular subsets due to the small number of eligible patients.
Review
Oncology
Paula Aldaz, Imanol Arozarena
Summary: Glioblastoma (GBM) is the most common and lethal form of malignant brain tumor, and patients typically undergo surgery followed by radiotherapy and chemotherapy. Despite promising preclinical evidence, clinical trials testing the therapeutic potential of tyrosine kinase inhibitors (TKIs) targeting EGFR, PDGF receptors, and other tyrosine kinases have not led to significant breakthroughs in treating GBM over the past two decades. This article critically analyzes the reasons for the failure of TKIs in GBM treatment and proposes alternative approaches for the evaluation of TKIs in GBM patients.
Article
Oncology
Ying-Chen Chen, Chu-Yen Chien, Chia-Chen Hsu, Chien-Hsing Lee, Yu-Ting Chou, Shine-Gwo Shiah, Shyun-Yeu Liu, Ching-Yu Yen, Alexander Cheng-Ting Hsieh, Martin Wabitsch, Yi-Shing Shieh
Summary: This study demonstrates that leptin-mediated AXL signaling pathway activation contributes to 5-FU resistance in colorectal cancer, suggesting a novel therapeutic strategy for colorectal cancer treatment.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Oncology
Sheena Bhalla, Farjana J. Fattah, Chul Ahn, Jessica Williams, Alyssa Macchiaroli, Jonathan Padro, Meredith Pogue, Jonathan E. Dowell, William C. Putnam, Nigel McCracken, David Micklem, Rolf A. Brekken, David E. Gerber
Summary: This study evaluated the efficacy and safety of bemcentinib in combination with docetaxel in advanced NSCLC patients. The results showed that bemcentinib plus docetaxel could inhibit tumor growth and produce partial responses in some patients.
Review
Biochemistry & Molecular Biology
Skye Montoya, Deborah Soong, Nina Nguyen, Maurizio Affer, Sailasya P. Munamarty, Justin Taylor
Summary: Development of targeted therapies has provided nonchemotherapeutic options for patients, with small molecule kinase inhibitors being a key focus. However, resistance to these therapies may develop, necessitating multiple lines of treatment. Combinations of therapies targeting complimentary pathways may be more effective in overcoming drug resistance.
Review
Biochemistry & Molecular Biology
Lizhuo Zhang, Qingqing Feng, Jiafeng Wang, Zhuo Tan, Qinglin Li, Minghua Ge
Summary: Thyroid cancer is a common endocrine malignant tumor, and surgery, chemotherapy, radiotherapy, and radioactive iodine therapy are the standard treatment modalities. However, multi-tyrosine kinase inhibitors and immune checkpoint inhibitors in combination with tyrosine kinase inhibitors have emerged as novel therapies for controlling the progression of thyroid cancer. This article discusses the molecular basis of thyroid cancer, reviews targeted therapeutic drugs in clinical research, and explores potentially novel molecular therapeutic targets.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Article
Medicine, Research & Experimental
Yuwen Zhu, Yan Guo, Yujia Xue, Anqi Zhou, Ying Chen, Yifei Chen, Xiulian Miao, Fangqiao Lv
Summary: BRG1 plays an important role in HSC-myofibroblast transition and targeting it could be a reasonable strategy for liver fibrosis intervention.
Article
Medicine, Research & Experimental
Liu Ye, Beibei Liu, Jingling Huang, Xiaolin Zhao, Yuan Wang, Yungen Xu, Shuping Wang
Summary: Doublecortin-like kinase 1 (DCLK1) is a significant prooncogenic factor that is strongly associated with the malignant progression and clinical prognosis of various cancers. DCLK1 plays important roles in stem cell marker regulation, tumor cell reprogramming, and immune evasion. However, the exact biological functions of DCLK1, especially the disparities between its alpha- and beta-form transcripts in cancer progression, remain ambiguous.
Article
Medicine, Research & Experimental
Jiahui Yang, Xiaoyu Chen, Tianjing Liu, Yongyan Shi
Summary: This article reviews the role of bile acids in necrotizing enterocolitis (NEC) and their potential therapeutic value. The dysregulation of bile acids is associated with intestinal injury, and inflammatory factors in the liver also play a crucial role in regulating bile acid transport. The bile acid metabolic pathway is important for regulating intestinal microbiota, cell proliferation, and barrier protection.
Review
Medicine, Research & Experimental
Zhenzheng Zhu, Yuemiao Xu, Yuwei Xia, Xinru Jia, Yixin Chen, Yuyue Liu, Leyin Zhang, Hui Chai, Leitao Sun
Summary: Bile acid, as the final product of cholesterol breakdown, plays a complex regulatory and signaling role in human metabolism. Research suggests that it has the potential to enhance metabolism and regulate chronic metabolic diseases through various pathways. The interaction between bile acid and gut microbiota is also of great significance.
Article
Medicine, Research & Experimental
Xin He, Hong-Xu Zhou, Xian Fu, Kai-Di Ni, Ai-Zhi Lin, Ling-Tong Zhang, Hou-Hua Yin, Qing Jiang, Xue Zhou, Yi-Wen Meng, Jun-Yan Liu
Summary: DON exposure causes an increase in deoxycholic acid (DCA), which contributes to intestinal injury. DCA may be a potential therapeutic target for DON enterotoxicity.
Article
Medicine, Research & Experimental
Zhitao Wang, Heng Ma, Abdul Nasir, Sufang Liu, Zhisong Li, Feng Tao, Qian Bai
Summary: This study reveals the involvement of TET1-mediated epigenetic regulation in chronic TMJ pain through trigeminal TNF alpha signaling.
Article
Medicine, Research & Experimental
Lu Yu, Hao Ran, Yaru Lu, Qian Ma, Huan Huang, Weibin Liu
Summary: This study found that the HIF-1 alpha inhibitor BAY 87-2243 can alleviate the symptoms of the Experimental Autoimmune Myasthenia Gravis (EAMG) inflammation model. BAY 87-2243 can restore the balance of CD4(+)T cell subsets, reduce the production of pro-inflammatory cytokines, and act as both an immune imbalance regulator and anti-inflammatory.
Article
Medicine, Research & Experimental
Alex Peralvarez-Marin, Montse Sole, Judith Serrano, Alice Taddeucci, Belen Perez, Clara Penas, Gemma Manich, Marcel Jimenez, Pilar D'Ocon, Francesc Jimenez-Altayo
Summary: This study provides the first evidence that TRPV2 channels may modulate vascular tone by balancing opposing inputs from the endothelium and smooth muscle, leading to net vasodilation. The amplification of TRPV2 channel-induced activity by NO emphasizes the pathophysiological relevance of these findings.
Article
Medicine, Research & Experimental
Amin Ullah, Jing Zhao, Jiakun Li, Rajeev K. Singla, Bairong Shen
Summary: Gastric cancer is the fifth-most prevalent and second-most deadly cancer worldwide. Late onset of symptoms makes early detection important. CXC chemokines play an important role in the pathological process of gastric cancer, but their exact role in diagnosis and prognosis is not fully understood. Inhibiting CXC chemokines shows promise as a targeted therapy.
Article
Medicine, Research & Experimental
Menna S. Zeyada, Salma M. Eraky, Mamdouh M. El-Shishtawy
Summary: The current study demonstrates the prophylactic and antifibrotic effects of Trig against BLM-induced PF by targeting multiple signaling pathways. The combination of Trig and Pirf may be a promising approach to enhance Pirf's anti-fibrotic effect.