Editorial Material
Hematology
Steven Grant
Summary: The identification and characterization of a novel cereblon-related E3 ligase modulator could have significant implications for the treatment of acute myelogenous leukemia, despite the established activity of cereblon-interacting agents in other hematologic malignancies.
Article
Pharmacology & Pharmacy
Jianbin Zhang, Yan Jiang, Ye Yu, Jiangping Li
Summary: This study evaluated the combination of TORC1/2 inhibitor sapanisertib and chemotherapy drug cisplatin for nasopharyngeal carcinoma (NPC) treatment. The results showed that sapanisertib effectively decreased NPC cell viability and proliferation, and acted synergistically with cisplatin to induce cell arrest and apoptosis. Sapanisertib had minimal effects on normal cells and also reduced NPC cell migration. These findings were evident in both in vitro and in vivo models.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Oncology
Ruyu Pi, Yang Yang, Xiaoyi Hu, Hongyi Li, Houhui Shi, Yu Liu, Xi Wang, An Tong, Tianqi Lu, Yuquan Wei, Xia Zhao, Xiawei Wei
Summary: High mTORC2 expression level in EOC is associated with poor prognosis, while AZD2014 inhibits tumor growth, reduces peritoneal ascites, and prolongs survival in tumor-bearing mice. In addition, AZD2014 also reduces MDSC accumulation and delays tumor recurrence in EOC models.
Article
Medicine, Research & Experimental
Yanping Wang, Yi Zhang, Shengchen Su, Patrick Tamukong, Ramachandran Murali, Hyung L. Kim
Summary: CD4+ regulatory T cells (Tregs) are crucial in controlling anti-tumor immune responses. A new PROTAC drug, PF, that targets the transcription factor FoxP3, has been developed. PF effectively decreases FoxP3 expression in Tregs, enhancing CD8+ lymphocyte proliferation and activation, as well as inhibiting tumor growth. PF also synergizes with immune checkpoint inhibitors and mTOR inhibitors to enhance antitumor immunity. This study provides important evidence for the potential use of PF in cancer immunotherapy.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Medicine, Research & Experimental
Alexander Zheleznyak, Matthew Mixdorf, Lynne Marsala, Julie Prior, Xiaoxia Yang, Grace Cui, Baogang Xu, Steven Fletcher, Francesca Fontana, Gregory Lanza, Samuel Achilefu
Summary: The study explores a new treatment approach targeting multiple myeloma, effectively inhibiting disease progression by simultaneously acting on cancer cells and bone cells. Experimental results demonstrate that this combination therapy significantly reduces tumor burden and prevents rapid relapse in mouse models.
Article
Cell Biology
Sheikh Tahir Majeed, Asiya Batool, Rabiya Majeed, Nadiem Nazir Bhat, Muhammad Afzal Zargar, Khurshid Iqbal Andrabi
Summary: Phosphorylated S209-eIF4E interacts with the TOS motif of S6K1, releasing it from auto-inhibition and priming it for activation in an mTORC1-independent manner. The role of mTORC1 is limited to engaging eIF4E with the S6K1-TOS motif to influence S6K1's state of activation.
Article
Oncology
Natasha Malik, Jodie Hay, Hassan N. B. Almuhanna, Karen M. Dunn, Jamie Lees, Jennifer Cassels, Jiatian Li, Rinako Nakagawa, Owen J. Sansom, Alison M. Michie
Summary: This study reveals the essential role of mTORC1 in the initiation/maintenance of leukemia in a CLL model and identifies the inactivation of eEF2 activity as a novel therapeutic target for blocking CLL progression.
Review
Oncology
Michal Grzmil, Fabius Wiesmann, Roger Schibli, Martin Behe
Summary: Targeted radionuclide therapy (TRT) is a cancer treatment that delivers cancer-selective radiopharmaceuticals to destroy cancer cells without harming healthy tissue. This review focuses on the use of mTORC1 inhibition to improve the efficacy of TRT by delivering radiolabeled ligands. It discusses the rationale, efficacy, and safety of this combinatorial approach in cancer patients.
Review
Genetics & Heredity
So Yeong Cheon, KyoungJoo Cho
Summary: Dysfunctional lipid metabolism can lead to metabolic disorders and inflammatory responses. The mTORC1 signaling pathway plays a key role in regulating lipid metabolism and immune responses, and may serve as a potential therapeutic target for metabolic disorders.
JOURNAL OF MOLECULAR MEDICINE-JMM
(2021)
Article
Environmental Sciences
Suchismita Daw, Sujata Law
Summary: The study examined the cellular signaling pathways and oxidative stress status in the bone marrow of MDS patients, and found that treatment with quercetin can improve autophagy process in cells, reduce oxidative damage, and restore the function of mitochondria and lysosomes.
ENVIRONMENTAL TOXICOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Silviu Stanciu, Florentina Ionita-Radu, Constantin Stefani, Daniela Miricescu, Iulia-Ioana Stanescu-Spinu, Maria Greabu, Alexandra Ripszky Totan, Mariana Jinga
Summary: Pancreatic cancer, although relatively rare, is becoming a leading cause of cancer death. Various risk factors, both modifiable and non-modifiable, contribute to its pathogenesis. Chronic inflammation plays a crucial role in the development of pancreatic cancer. The PI3K/AKT/mTOR signaling pathway is important in cell growth, survival, and motility.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
I-Lun Hsin, Huang-Pin Shen, Hui-Yi Chang, Jiunn-Liang Ko, Po-Hui Wang
Summary: The study revealed a novel mechanism of the PI3K/mTOR dual inhibitor, PQR309, in lowering cell viability in endometrial cancer cells by disrupting the PI3K/Akt/mTOR/c-Myc/mtp53 positive feedback loop.
Article
Medicine, Research & Experimental
Xin Wu, Zhongguang Wu, Woding Deng, Rong Xu, Chunmei Ban, Xiaoying Sun, Qiangqiang Zhao
Summary: Single-cell sequencing was used to analyze the composition of the bone marrow immune microenvironment in patients with acute myeloid leukaemia (AML), and the role of different subpopulations of T cells in the development of AML and in driving drug resistance was explored in conjunction with E3 ubiquitin ligase-related genes.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Biochemistry & Molecular Biology
Vincent Kuek, Anastasia M. Hughes, Rishi S. Kotecha, Laurence C. Cheung
Summary: Uniform prospective clinical trials have improved remission rates and survival for patients with acute myeloid leukaemia and acute lymphoblastic leukaemia in recent decades. However, high-risk patients continue to have inferior outcomes due to mechanisms where leukaemic cells hijack the bone marrow microenvironment. Targeting the cellular interactions within the leukaemia-bone marrow niche is an exciting novel strategy with significant potential to enhance treatment efficacy and improve patient outcomes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Meike Farber, Yiyang Chen, Lucas Arnold, Michael Moellmann, Eva Boog-Whiteside, Yu-An Lin, H. Christian Reinhardt, Ulrich Duehrsen, Maher Hanoun
Summary: Targeting the interaction between leukemic cells and the microenvironment by inhibiting CD38 has the potential to enhance therapeutic efficacy in AML. However, while the anti-CD38 antibody daratumumab showed significant cytostatic efficacy in an in vitro model, it ultimately lacked robust anti-leukemic effects in vivo in a xenograft transplantation model.
SCIENTIFIC REPORTS
(2021)