Review
Medicine, Research & Experimental
Soudeh Ghafouri-Fard, Hamed Shoorei, Atefe Abak, Sayed Haidar Abbas Raza, Martin Pichler, Mohammad Taheri
Summary: Paclitaxel is a chemotherapy drug used to treat various human malignancies, but resistance to it can occur. Non-coding RNAs have been found to influence cancer cell response to paclitaxel by regulating gene expression, particularly those involved in apoptosis. Targeted therapies against non-coding RNAs are suggested as effective modalities for combating resistance to paclitaxel.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Wilhelm Flat, Sarah Borowski, Themistoklis Paraschiakos, Christine Blechner, Sabine Windhorst
Summary: High DIAPH1 levels are correlated with increased survival of ovarian cancer patients. Down-regulation of DIAPH1 expression decreases PTX sensitivity and reduces the concentration of stable microtubules. In addition, DIAPH1 enhances the effect of PTX on microtubule stability in a cell-free system. Thus, DIAPH1 increases the response of Ovca cells to PTX.
BIOCHEMICAL PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Hend M. Nawara, Said M. Afify, Ghmkin Hassan, Maram H. Zahra, Akimasa Seno, Masaharu Seno
Summary: Paclitaxel is a commonly used chemotherapeutic agent that disrupts microtubule dynamics, induces mitotic arrest, and cell death. However, cancer resistance to paclitaxel is a major obstacle in clinical applications, and combining it with other drugs may lead to more efficient therapeutic strategies.
Article
Biochemistry & Molecular Biology
Maria Ovejero-Sanchez, Gloria Asensio-Juarez, Myriam Gonzalez, Pilar Puebla, Miguel Vicente-Manzanares, Rafael Pelaez, Rogelio Gonzalez-Sarmiento, Ana Belen Herrero
Summary: This study synthesized and characterized a new microtubule-destabilizing agent, PILA9, which showed strong cytotoxicity against OC cells. Additionally, the combination of microtubule-destabilizing agents with Panobinostat synergistically enhanced cytotoxicity, potentially through inducing alpha-tubulin acetylation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Celina Amaya, Shihua Luo, Julio Baigorri, Rogelio Baucells, Elizabeth R. Smith, Xiang-Xi Xu
Summary: Paclitaxel is a microtubule-stabilizing drug used for treating solid tumors like ovarian and breast cancer. Recent research suggests that low intensity ultrasound waves can prevent paclitaxel-induced cytotoxicity in cancer cells, by disrupting the microtubule cytoskeleton.
Article
Immunology
Tsong-Long Hwang, Chuan-Hsin Chang
Summary: This study aimed to determine whether oridonin enhances the anti-tumor activity of natural killer (NK) cells against lung cancer cells. The results showed that oridonin enhances NK cell cytotoxicity against A549 lung cancer cells by upregulating the expression of degranulation marker CD107a and IFN-γ, as well as activating NK cells and their ligand MICA/B. Oridonin also inhibits STAT3 phosphorylation in A549 cells and NK cells, and has a synergistic effect on the anti-tumor activity of NK cells.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Medicine, Research & Experimental
Jiezhu Feng, Zihan Peng, Lvfen Gao, Xiurou Yang, Zele Sun, Xiuying Hou, Enze Li, Linyan Zhu, Haifeng Yang
Summary: Over-expression of ClC-3 protein in PTX-resistant ovarian cancer cells promotes the combination of ClC-3 and beta-tubulin, reducing sensitivity to PTX.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Cell Biology
Zhao Liu, Du Meng, Jianling Wang, Hongxin Cao, Peng Feng, Siyu Wu, Na Wang, Chengxue Dang, Peng Hou, Peng Xia
Summary: GASP1 is highly expressed in breast cancer and its knockout inhibits malignant properties of breast cancer cells while improving their response to paclitaxel, indicating its potential as a therapeutic target in breast cancer.
CELL DEATH & DISEASE
(2022)
Article
Multidisciplinary Sciences
Francesca Amoroso, Kimberley Glass, Reema Singh, Francisco Liberal, Rebecca E. Steele, Sarah Maguire, Rohinton Tarapore, Joshua E. Allen, Sandra Van Schaeybroeck, Karl T. Butterworth, Kevin Prise, Joe M. O'Sullivan, Suneil Jain, David J. Waugh, Ian G. Mills
Summary: The study demonstrated that ONC201 can enhance the radiation response of prostate cancer cells by suppressing the expression of cell cycle and DNA repair factors.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Negin Riazi-Tabrizi, Mohammad Khalaj-Kondori, Sahar Safaei, Mohammad Amini, Hamidreza Hassanian, Mohadeseh Maghsoudi, Shima Hasani, Behzad Baradaran
Summary: Combination therapy of NRF2 siRNA with paclitaxel can significantly reduce NRF2 gene expression in pancreatic cancer cells, inhibiting cell migration, inducing apoptosis and autophagy, and arresting the cell cycle. NRF2 siRNA can also enhance the sensitivity of Miapaca-2 cells to paclitaxel, showing potential therapeutic efficacy in treating pancreatic cancer.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Anna Kleczka, Radoslaw Dzik, Agata Kabala-Dzik
Summary: This study investigated the effects of the combined use of caffeic acid phenethyl ester (CAPE) and paclitaxel (PTX) on ovarian cancer cells. The results showed that low doses of PTX exerted cytotoxic effects against all tested cell lines, and the combined use of CAPE and PTX enhanced the cytotoxicity and anti-migration activity.
Article
Biochemistry & Molecular Biology
Ying Li, Sisi Chen, Jianyu Zhu, Chanjuan Zheng, Muyao Wu, Lian Xue, Guangchun He, Shujun Fu, Xiyun Deng
Summary: Lovastatin may increase the sensitivity of drug-resistant prostate cancer cells to paclitaxel by inhibiting drug-metabolizing enzyme CYP2C8, serving as a chemosensitizer for paclitaxel-resistant prostate cancer cells.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Pharmacology & Pharmacy
Peng-Cheng Yu, Di Liu, Zeng-Xiang Han, Fang Liang, Cui-Yun Hao, Yun-Tao Lei, Chang-Run Guo, Wen-Hui Wang, Xing-Hua Li, Xiao-Na Yang, Chang-Zhu Li, Ye Yu, Ying-Zhe Fan
Summary: Thymopentin (TP5) is an immunomodulatory pentapeptide that inhibits the stemness of colon cancer cells and enhances the cytotoxicity of oxaliplatin (OXA). TP5 reduces stemness-related signals and alters Wnt/beta-catenin signaling by stimulating acetylcholine receptors (AchRs). This strategy provides promise for increasing sensitivity of colon cancer cells to chemotherapeutic agents.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Genetics & Heredity
Janani Ramesh, Rejani Chalikkaran Thilakan, Raja Mohan Gopalakrishnan, Singaravel Vijayapoopathi, Arianna Dorschel, Bhuvarahamurthy Venugopal
Summary: The study aimed to determine the potential of GRg5 as a chemosensitizer in PTX-resistant human cervical adeno-carcinoma cell lines (HeLa cells). The study found that GRg5 can enhance the cytotoxic effect of PTX in PTX-resistant HeLa cells by promoting the expression of Bax and activating caspase-9/-3, leading to apoptosis. Moreover, the study supports GRg5 as an inhibitor of Akt and NF-kappa B, which enhances the susceptibility of cervical cancer cells to PTX chemotherapy.
Article
Biochemistry & Molecular Biology
Klaire Yixin Fjaestad, Anne Mette Askehoj Romer, Victor Goitea, Astrid Zedlitz Johansen, Marie-Louise Thorseth, Marco Carretta, Lars Henning Engelholm, Lars Grontved, Niels Junker, Daniel Hargbol Madsen
Summary: The development of immune checkpoint inhibitors (ICI) has been an important breakthrough in cancer therapies, but only a limited number of patients benefit from them. Recently, the nonselective beta blocker propranolol has been shown to be effective in treating angiosarcoma and soft tissue sarcomas. It works by reducing tumor angiogenesis and promoting an anti-tumoral microenvironment with increased T cell infiltration. The combination of propranolol with immune checkpoint inhibitors can significantly enhance their efficacy.
Article
Oncology
Dengxuan Fan, Hailing Yang, Weiqun Mao, Philip J. Rask, Lan Pang, Congjian Xu, Hariprasad Vankayalapat, Ahmed A. Ahmed, Robert C. Bast, Zhen Lu
Summary: The study reveals that ARN-3261 can enhance the efficacy of paclitaxel and carboplatin in treating ovarian cancer by increasing their ability to kill cancer cells and decreasing survivin levels. Further clinical evaluation of ARN-3261 is warranted based on these preclinical findings.
Article
Oncology
Johannes F. Fahrmann, Ehsan Irajizad, Makoto Kobayashi, Jody Vykoukal, Jennifer B. Dennison, Eunice Murage, Ranran Wu, James P. Long, Kim-Anh Do, Joseph Celestino, Karen H. Lu, Zhen Lu, Robert C. Bast, Samir Hanash
Summary: The study identified a plasma polyamine signature associated with ovarian cancer that complemented CA125 in detecting early-stage ovarian cancer, providing potential markers for improving sensitivity in ovarian cancer detection. Mass spectrometry quantified four polyamines in plasma samples from ovarian cancer cases and controls, with a polyamine signature showing improved sensitivity and capturing cases missed by CA125 alone. This MYC-driven plasma polyamine signature offers promise for enhancing early ovarian cancer detection.
Editorial Material
Oncology
Anna Lokshin, Robert C. Bast, Karin Rodland
Article
Medicine, Research & Experimental
Mara Artibani, Kenta Masuda, Zhiyuan Hu, Pascal C. Rauher, Garry Mallett, Nina Wietek, Matteo Morotti, Kay Chong, Mohammad KaramiNejadRanjbar, Christos E. Zois, Sunanda Dhar, Salma El-Sahhar, Leticia Campo, Sarah P. Blagden, Stephen Damato, Pubudu N. Pathiraja, Shibani Nicum, Fergus Gleeson, Alexandros Laios, Abdulkhaliq Alsaadi, Laura Santana Gonzalez, Takeshi Motohara, Ashwag Albukhari, Zhen Lu, Robert C. Bast, Adrian L. Harris, Christer S. Ejsing, Robin W. Klemm, Christopher Yau, Tatjana Sauka-Spengler, Ahmed Ashour Ahmed
Summary: In this study, researchers found that minimal residual disease (MRD) cells in ovarian cancer patients share important molecular signatures with tumor-initiating cells (TICs), while also exhibiting an adipocyte-like gene expression signature and undergoing epithelial-mesenchymal transition (EMT). Through a cell culture MRD model, it was discovered that MRD-mimic cells are dependent on fatty acid oxidation (FAO) for survival and resistance to cytotoxic agents. These findings suggest that EMT and FAO could be potential targets for eradicating MRD in ovarian cancer and support further testing of FAO inhibitors for MRD treatment.
Article
Cell Biology
Jenny A. Rudnick, Teresa Monkkonen, Florie A. Mar, James M. Barnes, Hanna Starobinets, Juliet Goldsmith, Srirupa Roy, Sofia Bustamante Eguiguren, Valerie M. Weaver, Jayanta Debnath
Summary: Autophagy inhibitors are being explored for cancer treatment due to their ability to hinder tumor cell survival, while researchers are increasingly interested in how modulating autophagy in the host stroma affects tumorigenesis. Fibroblasts play key roles in cancer progression by promoting desmoplasia, with autophagy in stromal fibroblasts found to be crucial for mammary tumor growth.
GENES & DEVELOPMENT
(2021)
Article
Cell Biology
Sydney E. Cason, Peter J. Carman, Claire van Duyne, Juliet Goldsmith, Roberto Dominguez, Erika L. F. Holzbaur
Summary: The study identifies multiple dynein effectors that regulate the transport and maturation of autophagosomes in neurons, highlighting the tight link between maturation and transport. These findings provide insights into the maintenance of neuronal homeostasis and axonal health through the coordination of dynein-mediated processes.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Jasvinder Kaur, Juliet Goldsmith, Alexandra Tankka, Sofia Bustamante Eguiguren, Alfredo A. Gimenez, Lance Vick, Jayanta Debnath, Ariadne Vlahakis
Summary: The study reveals a previously unrecognized physiological role for yeast mitophagy in spermidine metabolism, showing that the adapter protein Atg32 is crucial for promoting spermidine production during respiratory growth and heat-induced mitochondrial stress. Mitophagy-deficient yeast exhibit defects in growth and viability during heat stress due to impaired biosynthesis of spermidine and its precursor S-adenosyl methionine, highlighting the importance of spermidine production for cytoprotective nitric oxide induction during heat stress.
JOURNAL OF CELL SCIENCE
(2021)
Article
Oncology
Chae Young Han, David A. Patten, Se Ik Kim, Jung Jin Lim, David W. Chan, Michelle K. Y. Siu, Youngjin Han, Euridice Carmona, Robin J. Parks, Cheol Lee, Li-Jun Di, Zhen Lu, Karen K. L. Chan, Ja-Lok Ku, Elizabeth A. Macdonald, Barbara C. Vanderhyden, Anne-Marie Mes-Masson, Hextan Y. S. Ngan, Annie N. Y. Cheung, Yong Sang Song, Robert C. Bast, Mary-Ellen Harper, Benjamin K. Tsang
Summary: This study highlights the functional interaction between HKII and activated P-p53 (Ser15) in the regulation of bioenergetics and chemosensitivity, emphasizing the increased nuclear HKII-P-p53 (Ser15) interaction as a potential prognostic biomarker in ovarian cancer.
Review
Oncology
Gamze Bildik, Xiaowen Liang, Margie N. Sutton, Robert C. Bast, Zhen Lu
Summary: DIRAS3 is an imprinted tumor suppressor gene that blocks RAS function, inhibits malignant transformation and cancer cell growth, and facilitates the survival of dormant cancer cells. Downregulation of DIRAS3 expression is associated with various cancers and can serve as a target for novel therapy after conventional treatment.
MOLECULAR CANCER THERAPEUTICS
(2022)
Article
Neurosciences
Juliet Goldsmith, Alban Ordureau, J. Wade Harper, Erika L. F. Holzbaur
Summary: This study reveals the importance of autophagy in maintaining neuronal health. By isolating autophagic vesicles and using proteomics, the researchers identified mitochondrial proteins as a major cargo engulfed in autophagosomes. They also found that nucleoid-associated proteins are enriched in autophagic engulfment of nucleoid-enriched mitochondrial fragments, and this process requires the mitochondrial fission machinery protein Drp1.
Article
Oncology
Kristin L. M. Boylan, Ashley Petersen, Timothy K. Starr, Xuan Pu, Melissa A. Geller, Robert C. Bast, Karen H. Lu, Ugo Cavallaro, Denise C. Connolly, Kevin M. Elias, Daniel W. Cramer, Tanja Pejovic, Amy P. N. Skubitz
Summary: This study aimed to develop a multiprotein classifier for detecting early stages of ovarian cancer by analyzing the levels of 92 cancer-related proteins in the blood. The combination of four proteins successfully detected over 90% of women with ovarian cancer and improved sensitivity and specificity compared to using CA125 alone. These findings suggest potential new biomarkers for early stage ovarian cancer detection.
Article
Medicine, Research & Experimental
Zhen Lu, Weiqun Mao, Hailing Yang, Janice M. Santiago-O'Farrill, Philip J. Rask, Jayanta Mondal, Hu Chen, Cristina Ivan, Xiuping Liu, Chang-Gong Liu, Yuanxin Xi, Kenta Masuda, Eli M. Carrami, Meng Chen, Yitao Tang, Lan Pang, David S. Lakomy, George A. Calin, Han Liang, Ahmed A. Ahmed, Hariprasad Vankayalapati, Robert C. Bast
Summary: PARP inhibitors selectively target cancer cells with homologous recombination DNA repair deficiency, but resistance eventually develops. SIK2 inhibitors have been found to enhance the sensitivity of ovarian and triple-negative breast cancer cells to PARP inhibitors through suppressing DNA repair functions and gene transcription.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Na Niu, Jun Yao, Robert C. Bast, Anil K. Sood, Jinsong Liu
Summary: The research revealed that IL-6 plays a crucial role in the formation and transformation of PGCCs into CAFs, and blocking IL-6 can attenuate tumor growth and inhibit drug resistance.
Article
Chemistry, Multidisciplinary
Joshua P. Gray, Md. Nasir Uddin, Rajan Chaudhari, Margie N. Sutton, Hailing Yang, Philip Rask, Hannah Locke, Brian J. Engel, Nefeli Batistatou, Jing Wang, Brian J. Grindel, Pratip Bhattacharya, Seth T. Gammon, Shuxing Zhang, David Piwnica-Worms, Joshua A. Kritzer, Zhen Lu, Robert C. Bast, Steven W. Millward
Summary: Autophagy induction has been found to play a crucial role in the development of treatment resistance and dormancy in various cancer types. Current autophagy inhibitors, such as chloroquine and hydroxychloroquine, face challenges of poor pharmacokinetics and high toxicity at therapeutic dosages. Through the use of Scanning Unnatural Protease Resistant (SUPR) mRNA display, macrocyclic peptides targeting the autophagy protein LC3 were developed, showing promising results in sensitizing platinum-resistant ovarian cancer cells to chemotherapy. These peptides disrupted protein-protein interactions and inhibited autophagic flux, leading to significant tumor growth inhibition in mouse models of metastatic ovarian cancer.