Article
Pharmacology & Pharmacy
Bihui Li, Xing Zhang, Qianyao Ren, Li Gao, Jing Tian
Summary: Despite promising results in vitro and preclinical studies, the dual PI3K/Akt/mTOR inhibitor NVP-BEZ235 and the ATP-competitive mTOR inhibitor PP242 failed to show inhibitory efficacy against renal cell carcinoma (RCC) in clinical settings. However, they both demonstrated marked effects by targeting TAK1-dependent pathways in RCC cells, especially NVP-BEZ235, suggesting potential application in combination therapy for RCC.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cell Biology
Shreya Udawant, Carl Litif, Alma Lopez, Bonnie Gunn, Erin Schuenzel, Megan Keniry
Summary: The study compared the role of the PI3K/AKT/mTOR pathway in GBM tumor metabolism, revealing that PI3K-impacted glycolytic genes are over-expressed and associated with poor prognosis in GBM patients.
Article
Oncology
Jie Li, Xiaozi Wang, Chuanbao Ma, Shasha Xu, Mengyao Xu, Jie Yang, Ruicang Wang, Liying Xue
Summary: BEZ235 effectively reduces cell viability, induces cell cycle arrest and increases apoptosis in Doxo-resistant K562/A cells. It achieves this by inhibiting the PI3K/AKT/mTOR pathway, providing a potential therapeutic approach for leukemia cells.
MOLECULAR MEDICINE REPORTS
(2021)
Article
Cell Biology
Yao Wang, Xiaolong Miao, Yuancong Jiang, Zelai Wu, Xuhang Zhu, Han Liu, Xiaoying Wu, Jinzhen Cai, Xianfeng Ding, Weihua Gong
Summary: In this study, the combination of anti-IL-6 antibody and NVP-BEZ235 showed enhanced antitumor effects in hepatocellular carcinoma (HCC) by synergistically inhibiting the PI3K/AKT/mTOR signaling pathway. These findings provide guidance for the analysis and clinical treatment of HCC.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
H. Jonathan G. Lindstrom, Ran Friedman
Summary: Targeted therapies for CML are effective but rarely curative. Drug resistance is a major cause of death in CML, and preventing resistance is crucial. Drug rotation has been theorized as a way to delay resistance, and in vitro testing has shown some promising results in a CML cell line.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Yun Xu, Ziting Wang, Lei Zhang, Congying Gao, Fahui Li, Xueming Li, Yu Ke, Hong-Min Liu, Zhenbo Hu, Liuya Wei, Zhe-Sheng Chen
Summary: The compound JOA can inhibit the proliferation of chronic myeloid leukemia cells, including those with the BCR-ABL-T315I mutation, and induce cell differentiation. This effect may be mediated by the inhibition of the BCR-ABL/c-MYC signaling pathway. JOA shows potential as a lead compound for overcoming imatinib resistance in CML therapy.
Article
Immunology
Saeid Taghiloo, Abolghasem Ajami, Reza Alizadeh-Navaei, Hossein Asgarian-Omran
Summary: This study found that combination therapy with BEZ235 and R848 significantly improved the immune system function of AML mice and reduced the number of tumor immune suppressor cells. Following treatment, the mice experienced significant improvements in organomegaly, body weight, and survival rate.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Narissa Parry, Caroline Busch, Victoria Assmann, Jennifer Cassels, Alan Hair, G. Vignir Helgason, Helen Wheadon, Mhairi Copland
Summary: Dysregulation of the BCL-2 family is implicated in protecting CML cells, making it a viable therapeutic target. BH3 mimetics show clinical promise in the treatment of CML and can be used in combination with standard therapies. Combination of TKIs and BH3 mimetics significantly reduces cell viability and induces apoptosis in BP-CML cells. BH3 mimetics are more effective in myeloid BP-CML compared to single treatment.
CELL DEATH DISCOVERY
(2022)
Article
Pharmacology & Pharmacy
Cagla Kayabasi, Besra Ozmen Yelken, Aycan Asik, Tugce Balci Okcanoglu, Fatma Sogutlu, Roya Gasimli, Sunde Yilmaz Susluer, Guray Saydam, Cigir Biray Avci, Cumhur Gunduz
Summary: The study evaluated the potential of ponatinib and PI3K/mTOR dual-inhibitor VS-5584 combination therapy to selectively eliminate CML cells and LSCs, highlighting the promising anti-leukemic effects of PoVS with reduced doses of ponatinib.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Oncology
Li Zhang, Li Meng, Bingcheng Liu, Yanli Zhang, Huanling Zhu, Jiuwei Cui, Aining Sun, Yu Hu, Jie Jin, Hao Jiang, Xi Zhang, Yan Li, Li Liu, Wanggang Zhang, Xiaoli Liu, Jian Gu, Jianhui Qiao, Guifang Ouyang, Xin Liu, Jianmin Luo, Ming Jiang, Xiaobao Xie, Jianyong Li, Chunting Zhao, Mei Zhang, Tonghua Yang, Jianxiang Wang
Summary: Flumatinib demonstrated significantly higher rates of response, faster, and deeper responses compared to imatinib in the first-line treatment of chronic phase Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP).
CLINICAL CANCER RESEARCH
(2021)
Review
Oncology
Anna Sicuranza, Donatella Raspadori, Monica Bocchia
Summary: CD26/DPP-4 is a membrane-bound multifunctional protein that is expressed in many solid tumors and hematological malignancies, and recent investigations have shown its specific expression on leukemic stem cells of Chronic Myeloid Leukemia. This finding suggests that CD26 could be a potential marker for monitoring therapeutic responses in CML patients receiving Tyrosine Kinase Inhibitors treatment. Preliminary data from a multicenter study in Italy indicated that CML patients with a poorer response had a higher number of CD26+ LSCs at diagnosis, confirming the specificity of CD26 as a marker in CML.
Review
Hematology
Naranie Shanmuganathan, Timothy P. Hughes
Summary: The recent approval of asciminib as a treatment option for CML patients provides clinicians with more choices for therapy. Asciminib is a highly potent BCR-ABL1 inhibitor with limited off-target effects, but its position among other available TKIs is still unclear. There are many unanswered questions about the optimal use of asciminib.
BRITISH JOURNAL OF HAEMATOLOGY
(2022)
Article
Oncology
Cagla Kayabasi, Sunde Yilmaz Susluer, Tugce Balci Okcanoglu, Besra Ozmen Yelken, Zeynep Mutlu, Bakiye Goker Bagca, Cansu Caliskan Kurt, Guray Saydam, Cenk Durmuskahya, Husniye Kayalar, Ahmet Ozbilgin, Cigir Biray Avci, Cumhur Gunduz
Summary: Origanum sipyleum extract (OSM), containing terpenoids, flavonoids, tannins, and anthracenes, exhibited cytotoxic effects on chronic myeloid leukemia (CML) cells. When combined with ponatinib (a tyrosine kinase inhibitor), OSM showed synergistic effects and reduced the dose of ponatinib. Furthermore, OSM enhanced the anti-leukemic activity of ponatinib by inducing apoptosis, suppressing proliferation, and regulating the cell cycle.
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
(2022)
Article
Health Care Sciences & Services
Valentina Perrone, Elisa Giacomini, Margherita Andretta, Loredana Arenare, Maria Rosaria Cillo, Marisa Latini, Alessandra Mecozzi, Romina Pagliaro, Adriano Vercellone, Luca Degli Esposti
Summary: This observational retrospective study in Italy evaluated the mean daily dose of nilotinib prescribed for first- and second-line therapy in chronic myeloid leukemia patients. The study found that the real-world dosage of nilotinib prescribed in clinical practice settings was lower than the dosage currently indicated in the datasheet.
THERAPEUTICS AND CLINICAL RISK MANAGEMENT
(2021)
Article
Pharmacology & Pharmacy
Congying Gao, Lei Zhang, Yun Xu, Xiangyu Ma, Peilei Chen, Zhe-Sheng Chen, Liuya Wei
Summary: In this study, the potent histone deacetylase inhibitor I13 was assessed for its effect on chronic myeloid leukemia (CML) cells harboring T315I-mutated and wild-type BCR-ABL. I13 showed strong activity against both types of cells, inducing cell differentiation and suppressing proliferation by causing cell cycle G0/G1-phase accumulation. It was found that I13 blocked the CML signaling pathway by depleting BCR-ABL, resulting in cell differentiation. These findings highlight I13 as a BCR-ABL modulator for overcoming drug resistance caused by T315I-mutated BCR-ABL and have implications for CML therapy development.
FRONTIERS IN PHARMACOLOGY
(2023)