Article
Oncology
Adi Knigin, Shani Avniel-Polak, Gil Leibowitz, Kira Oleinikov, David J. Gross, Simona Grozinsky-Glasberg
Summary: In advanced stage lung neuroendocrine neoplasms, treatment options are limited. The mTOR inhibitor everolimus can paradoxically encourage cancer cell survival. Chloroquine, an autophagy inhibitor, suppresses tumor cell growth and enhances the effects of mTOR inhibitors. More research is needed to explore the potential role of chloroquine in treating patients with advanced lung neuroendocrine neoplasms.
Article
Medicine, Research & Experimental
Stefania Cocco, Alessandra Leone, Maria Serena Roca, Rita Lombardi, Michela Piezzo, Roberta Caputo, Chiara Ciardiello, Susan Costantini, Francesca Bruzzese, Maria Jose Sisalli, Alfredo Budillon, Michelino De Laurentiis
Summary: The study found that two PI3K/AKT inhibitors, ipatasertib and taselisib, induced autophagy signaling in different breast cancer models. This effect was particularly evident in PI3K/AKT resistant TNBC cells, where the inhibition of autophagy by CQ potentiated the therapeutic effect of PI3K/AKT inhibitors in vitro and in vivo TNBC models, synergizing with taxane-based chemotherapy.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Oncology
Samantha Exner, Gerard Arrey, Vikas Prasad, Carsten Groetzinger
Summary: mTOR inhibitors demonstrate significant growth inhibition in NEN cell lines and have been shown to have radiosensitizing effects, showing potential in improving treatment efficacy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Nienke Visser, Harm Jan Lourens, Gerwin Huls, Edwin Bremer, Valerie R. Wiersma
Summary: The study found that the activity of the autophagy pathway did not differ between AraC-Res AML cells and parental AraC-sensitive AML cells, and treatment with autophagy inhibitors did not re-sensitize AraC-Res AML cells to AraC. However, in parental AraC-sensitive AML cells, treatment with AraC activated autophagy and a combination with autophagy inhibitors significantly reduced cell viability. Additionally, the combination of these drugs resulted in the highest level of cell death in patient-derived AML samples, although not additive.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Charalampos Aktypis, Maria-Eleni Spei, Maria Yavropoulou, Goran Wallin, Anna Koumarianou, Gregory Kaltsas, Eva Kassi, Kosmas Daskalakis
Summary: This study provides a comprehensive review of the safety profile of biotherapy and molecular targeted therapies in NEN patients, focusing on cardiovascular toxicities. Results indicate that SSAs and TPH inhibitors are safer in terms of overall toxicity, particularly cardiovascular toxicities, compared to mTOR inhibitors and TKIs.
Review
Medicine, Research & Experimental
Manasi P. Jogalekar, Anurag Veerabathini, Prakash Gangadaran
Summary: Autophagy plays a crucial role in cellular development, diseases, and cancer. Various autophagy modulators have been developed and shown promising results in preclinical trials.
EXPERIMENTAL BIOLOGY AND MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ying-Yue Yang, Wan-Li Wang, Xia-Tong Hu, Xin Chen, Yang Ni, Yan-Hua Lei, Qi-Yuan Qiu, Long-Yue Tao, Tian -Wen Luo, Ning-Yu Wang
Summary: The mammalian target of rapamycin (mTOR) has been proven to be an effective target for cancer therapy. Rapalogs and mTOR kinase inhibitors (TORKi) have been developed and clinically validated in several types of malignancies, with TORKi showing better antitumor activity by inhibiting both mTORC1 and mTORC2. However, the clinical development of current TORKi candidates has been relatively slow, and there is a need to develop more TORKi with novel scaffold to expand the current pipelines.
BIOORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Tian Xu, Jifa Zhang, Chengcan Yang, Ryszard Pluta, Guan Wang, Tinghong Ye, Liang Ouyang
Summary: This study identified a potential compound for treating triple negative breast cancer by screening mTOR inhibitors and studying their related activities. The compound was found to induce apoptosis and autophagic cell death in cancer cells, providing new insights for future drug development for TNBC treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Veterinary Sciences
Gianmarco Ferrara, Consiglia Longobardi, Sara Damiano, Roberto Ciarcia, Ugo Pagnini, Serena Montagnaro
Summary: This study aims to investigate the involvement of the PI3K/Akt/mTOR pathway during FeHV-1 infection. The results suggest that FeHV-1 may interact independently with different autophagic signaling pathways. Additionally, early phosphorylation of Akt after infection may be related to viral entry.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Article
Oncology
Maryam Safari, Luigi Scotto, Thomas Litman, Lubov A. Petrukhin, Hu Zhu, Min Shen, Robert W. Robey, Matthew D. Hall, Tito Fojo, Susan E. Bates
Summary: By screening two drug libraries, NAMPT and HDAC inhibitors were identified as the most active agents against neuroendocrine tumor-derived cell lines. Inhibition of NAMPT led to a reduction in basal oxidative phosphorylation and energy production, partially mediated by the involvement of YAP1. Combining NAMPT and HDAC inhibitors showed synergistic effects and could be an effective treatment for neuroendocrine neoplasms.
Article
Pharmacology & Pharmacy
Keagan P. Collins, Sandra Witta, Jonathan W. Coy, Yi Pang, Daniel L. Gustafson
Summary: This study found that modulating lysosomal volume can affect the metabolism of hydroxychloroquine (HCQ), a lysosomotropic agent, and that pretreatment with TFEB-activating agent increased whole-cell HCQ concentrations. Through the use of an in vitro pharmacokinetic model, the role of lysosomal dynamics in lysosomotropic drug metabolism was elucidated, advancing our understanding of lysosomal-mediated multiple drug resistance and drug-drug interactions.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Sami Matrood, Leander Edwin Melms, Detlef Klaus Bartsch, Pietro Di Fazio
Summary: This study aims to investigate the association between the expression of autophagy-associated gene transcripts and clinical parameters in pNEN. The results show that G1 sporadic pNEN have higher expression of autophagic genes compared to G2, and pNEN with decreased expression of autophagic genes are more likely to have lymphatic and distant metastasis. Insulinomas have higher levels of autophagic transcripts compared to gastrinomas and non-functional pNEN. MEN1-associated pNEN exhibit higher expression of autophagic genes than sporadic pNEN.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Tingting Feng, Ruibin Jiang, Lu Yin, Chenyang Xu, Jian Ma, Wenjuan Yin, Jiaoyue Jin, Tingting Lu, Xinyuan Liu, Yingqi Lyu, Ying Yang, Lisha Ying, Qichao Hu, Dan Su, Sunbin Ling
Summary: This study found that PBK is significantly upregulated in pNEN tissues and is a poor prognostic factor for pNEN patients. PBK promotes the proliferation of pNEN cells by activating the AKT/mTOR pathway. Inhibition of PBK combined with everolimus treatment enhances the antitumour effects on pNEN by inhibiting the AKT/mTOR pathway and inducing cell cycle arrest.
MOLECULAR CARCINOGENESIS
(2023)
Review
Pharmacology & Pharmacy
Alexander G. Raufi, Nicholas R. Liguori, Lindsey Carlsen, Cassandra Parker, Liz Hernandez Borrero, Shengliang Zhang, Xiaobing Tian, Anna Louie, Lanlan Zhou, Attila A. Seyhan, Wafik S. El-Deiry
Summary: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with slow progress towards effective therapy, indicating an urgent need for novel treatment approaches, with autophagy potentially being a promising therapeutic target.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Bing Jiang, Longfei Feng, Tao Yang, Wenjing Guo, Yangyang Li, Tao Wang, Chengguang Liu, Haixiang Su
Summary: Hepatocellular carcinoma (HCC) is the leading cause of cancer-associated death worldwide, and chemotherapy is the primary treatment method. Salidroside (Sal), a bioactive component from Rhodiola rosea L, has been shown to induce apoptosis and autophagy in HCC cells. Sal enhances apoptosis and autophagy by regulating the expression of various proteins and inhibits the PI3K/Akt/mTOR signaling pathway. Furthermore, combining Sal with the autophagy inhibitor chloroquine diphosphate (CQ) can decrease Sal-induced autophagy and accelerate Sal-induced apoptosis.
MOLECULAR MEDICINE REPORTS
(2023)