Article
Oncology
Valeria Sanabria Guillen, Yvonne Ziegler, Chirag Gopinath, Sandeep Kumar, Parama Dey, Blake N. Plotner, Nadia Z. Dawson, Sung Hoon Kim, John A. Katzenellenbogen, Benita S. Katzenellenbogen
Summary: There are currently limited treatment options for patients with advanced breast cancer. The oncogenic transcription factor FOXM1 plays a role in all subtypes of breast cancer. By combining FOXM1 inhibitors with other drugs, it may be possible to enhance the effectiveness of treatment for breast cancer.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Biochemistry & Molecular Biology
Shi-Xiong Liu, Yun Zhou, Li Zhao, Ling -Shan Zhou, Jie Sun, Ge-Jing Liu, Ying-Shi Du, Yong-Ning Zhou
Summary: The study found that FOXM1 expression levels were significantly up-regulated in human gastric cancer cell lines and tissues, and its expression was higher in patients with metastasis. Suppression of FOXM1 with its inhibitor THIO significantly inhibited the proliferation of gastric cancer cells, induced apoptosis, and suppressed migration, invasion, and angiogenesis. Furthermore, THIO promoted drug-resistant gastric cancer cells to chemotherapies and inhibited the epithelial-mesenchymal transition (EMT) process. These findings suggest that FOXM1 is a promising therapeutic target for gastric cancer treatment and THIO has potential as a therapeutic agent for the disease.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Chemistry, Multidisciplinary
Hamadi Madhi, Jeon-Soo Lee, Young Eun Choi, Yan Li, Myoung Hee Kim, Yongdoo Choi, Sung-Ho Goh
Summary: The focus of this study is FOXM1, which is identified as a potential therapeutic target for cancer immunotherapy and associated with the modulation of PD-L1 expression. The study found that selective knockdown of FOXM1 or treatment with TST significantly reduces PD-L1 expression in NSCLC cells and inhibits proliferation. Animal studies showed that TST treatment downregulates PD-L1 expression in NSCLC tumors and reduces tumor size without side effects. Combined treatment with TST and anti-4-1BB antibody induces synergistic therapeutic outcomes against immune resistant lung tumors and increases the number of CD3(+) T cells in tumor tissues.
Article
Chemistry, Multidisciplinary
Wen-die Wang, Yue Shang, Chen Wang, Jun Ni, Ai-min Wang, Gao-jie Li, Ling Su, Shu-zhen Chen
Summary: This study investigated the effects of c-FLIP on the expression and ubiquitination levels of FoxM1 in non-small-cell lung cancer (NSCLC) cells, and explored the role of c-FLIP/FoxM1 in drug resistance. The findings demonstrated that c-FLIP stabilized FoxM1 by inhibiting its ubiquitination, and promoted the resistance of NSCLC cells to thiostrepton and osimertinib by upregulating FoxM1. The combination of FoxM1 and c-FLIP was found to be a more accurate prognostic biomarker for NSCLC patients.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Oncology
Luzie Bruckner, Annika Reinshagen, Ngoc Anh Hoang, Anne Kathrin Hoehn, Florian Lordick, Ingo Bechmann, Bahriye Aktas, Ivonne Nel, Sonja Kallendrusch
Summary: Late diagnosis and resistance to therapy are major reasons for the high mortality rate of ovarian cancer. A model system was developed to predict individual treatment susceptibility and the potential benefit of FOXM1 inhibition in ovarian cancer was demonstrated through tissue cultures.
Review
Pharmacology & Pharmacy
Zahra Alimardan, Maryam Abbasi, Farshid Hasanzadeh, Mahmud Aghaei, Ghadamali Khodarahmi, Khosrow Kashfi
Summary: Heat shock proteins (Hsps), including Hsp70, Hsp90, and small Hsps, and the transcription factor FoxM1, have important roles in carcinogenesis. Hsp70 functions in cancer initiation and protein folding, and is overexpressed in human cancers. It also interacts with cochaperones and regulates the FoxM1 signaling pathway. FoxM1 is overexpressed in most human cancers and is involved in various cancer-related processes. This review covers the structure, function, and inhibitors of Hsp70, Hsp90, and FoxM1.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Jinhai Wang, Ying Fang, R. Andrea Fan, Christopher J. Kirk
Summary: The proteasome plays a crucial role in tumor and immune cell biology, serving as a therapeutic target for drug development. Various inhibitors have been approved for the treatment of multiple myeloma, with ongoing development of selective immunoproteasome inhibitors for autoimmune diseases. Researchers compare the pharmacokinetics, pharmacodynamics, and metabolism of these compounds, highlighting the distinct metabolism pathway of peptide epoxyketones as a favorable property for chronic conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Shilpa Kuttikrishnan, Kirti S. Prabhu, Abdul Q. Khan, Feras Q. Alali, Aamir Ahmad, Shahab Uddin
Summary: The study showed that downregulation of FoxM1 by its inhibitor thiostrepton inhibited cell viability and induced caspase-dependent apoptosis in B-pre-ALL cell lines. Thiostrepton led to downregulation of FoxM1 and multiple cancer-related genes, increased Bax/Bcl2 ratio, and suppression of antiapoptotic proteins. Co-treatment of B-pre-ALL with subtoxic doses of thiostrepton and bortezomib potentiated proapoptotic action, suggesting that targeting FoxM1 expression could be an attractive strategy for B-pre-ALL treatment.
LEUKEMIA & LYMPHOMA
(2021)
Article
Multidisciplinary Sciences
Mengmeng Dong, Jinna Zhang, Xiaoyan Han, Jingsong He, Gaofeng Zheng, Zhen Cai
Summary: This study retrospectively analyzed clinical data of 155 MM patients and found that baseline PN was age-related, leading to more severe BiPN during bortezomib induction therapy and worse PN outcome after induction therapy. MM patients with baseline PN also had worse PFS and OS.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Markus Klein, Michael Busch, Manja Friese-Hamim, Stefano Crosignani, Thomas Fuchss, Djordje Musil, Felix Rohdich, Michael P. Sanderson, Jeyaprakashnarayanan Seenisamy, Gina Walter-Bausch, Ugo Zanelli, Philip Hewitt, Christina Esdar, Oliver Schadt
Summary: Proteasomes are essential components of the ubiquitin-dependent protein degradation pathway, with LMP7 being a subunit of the immunoproteasome. Current pan-proteasome inhibitors nonselectively target LMP7 and other subunits, limiting their therapeutic applicability. Novel amido boronic acids were discovered to selectively inhibit LMP7, leading to the identification of the highly potent and orally available inhibitor M3258, which showed strong antitumor activity in MM models.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Review
Oncology
Priyanka S. Rana, James J. Ignatz-Hoover, James J. Driscoll
Summary: Proteasomes are complex protein-degrading machines that regulate the elimination of intracellular proteins. Immunoproteasomes are a specialized variant that degrade proteins in cells exposed to oxidative stress and inflammation. They can be targeted for therapeutic purposes in the treatment of cancer and infectious diseases.
Review
Chemistry, Multidisciplinary
Andressa Barban do Patrocinio, Vanderlei Rodrigues, Lizandra Guidi Magalhaes
Summary: This review discusses the mechanism of protein p53 degradation through the ubiquitin-proteasome system, and how compounds inhibiting the 26S proteasome can treat cancer and other diseases by regulating the stability of p53.
Article
Chemistry, Multidisciplinary
Wenhu Zhan, Hao Zhang, John Ginn, Annie Leung, Yi J. Liu, Mayako Michino, Akinori Toita, Rei Okamoto, Tzu-Tshin Wong, Toshihiro Imaeda, Ryoma Hara, Takafumi Yukawa, Sevil Chelebieva, Patrick K. Tumwebaze, Maria Jose Lafuente-Monasterio, Maria Santos Martinez-Martinez, Jeremie Vendome, Thijs Beuming, Kenjiro Sato, Kazuyoshi Aso, Philip J. Rosenthal, Roland A. Cooper, Peter T. Meinke, Carl F. Nathan, Laura A. Kirkman, Gang Lin
Summary: Studies have shown that Plasmodium falciparum proteasome inhibitors have the potential to treat, prevent, and block transmission of malaria. A noncovalent, macrocyclic peptide inhibitor with high species selectivity and improved pharmacokinetic properties has been developed, demonstrating specific inhibition of the Pf20S beta 5 subunit.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Review
Biochemistry & Molecular Biology
Sanjeev Raghuwanshi, Andrei L. Gartel
Summary: This review discusses the role and therapeutic potential of FOXM1 protein in cancer. FOXM1 plays a critical role in cell proliferation, migration, invasion, angiogenesis, and metastasis in cancer cells, and is also associated with chemoresistance. Inhibition of FOXM1 can enhance the sensitivity of cancer cells to drugs, making small molecule inhibitors targeting FOXM1 a potential novel strategy for treating chemo-resistant cancers.
BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER
(2023)
Review
Pharmacology & Pharmacy
Agata Kodron, Ben Hur Mussulini, Iwona Pilecka, Agnieszka Chacinska
Summary: Proteasome dysfunction can lead to protein toxicity and mitochondrial dysfunction, while mitochondrial impairment can cause protein oxidation and misfolding leading to proteasome overload.
PHARMACOLOGICAL RESEARCH
(2021)
