Article
Oncology
Irene Veneziani, Paola Infante, Elisa Ferretti, Ombretta Melaiu, Cecilia Battistelli, Valeria Lucarini, Mirco Compagnone, Carmine Nicoletti, Aurora Castellano, Stefania Petrini, Marzia Ognibene, Annalisa Pezzolo, Lucia Di Marcotullio, Roberto Bei, Lorenzo Moretta, Vito Pistoia, Doriana Fruci, Vincenzo Barnaba, Franco Locatelli, Loredana Cifaldi
Summary: The study demonstrated that Nutlin-3a could enhance NK cell-mediated killing of neuroblastoma cells by restoring p53 function and increasing ligand expression for NK-ARs. Adoptive transfer of human NK cells into neuroblastoma-bearing mice resulted in tumor shrinkage and improved overall survival. Nutlin-3a also boosted NK cell-mediated cytotoxicity against neuroblastoma spheroids by increasing ligand expression in primary neuroblastoma cells.
CANCER IMMUNOLOGY RESEARCH
(2021)
Article
Oncology
Konstantina Psatha, Laxmikanth Kollipara, Elias Drakos, Elena Deligianni, Konstantinos Brintakis, Eustratios Patsouris, Albert Sickmann, George Z. Rassidakis, Michalis Aivaliotis
Summary: The activation of wild-type p53 protein in human lymphoma is a promising therapeutic strategy. An in vitro integrative comparative multi-omics analysis of different lymphoma types before and after p53 activation can shed light on the molecular mechanisms involved. Our findings provide valuable insights into the role of specific proteins and pathways in lymphoma pathogenesis and the global effect of nutlin-3a, which can guide targeted studies on lymphoma progression and resistance.
Article
Cell Biology
Rasoul Pourebrahim, Rafael Heinz Montoya, Zoe Alaniz, Lauren Ostermann, Patrick P. Lin, Bin Liu, Edward Ayoub, Jared K. Burks, Michael Andreeff
Summary: Mesenchymal stromal cells (MSCs) play a crucial role in supporting hematopoietic stem cells in the bone marrow (BM) niche. This study demonstrates the essential function of Mdm2 in the emergence, maintenance, and hematopoietic support of BM-MSCs. Additionally, the p53 pathway is shown to be involved in the survival and protection of BM-MSCs in acute myeloid leukemia (AML) against hematopoietic toxicity caused by MDM2is. These findings provide new insights into the mechanism of MDM2is-induced hematopoietic toxicity.
CELL DEATH & DISEASE
(2023)
Review
Medicine, Research & Experimental
Charlie Marvalim, Arpita Datta, Soo Chin Lee
Summary: The transcription factor p53 plays a crucial role in regulating cellular processes and is activated in response to genotoxic stress. In breast cancer, p53's tumor suppressive activities are often compromised by the overexpression of MDM2 or mutation, with the latter being more common in hormone receptor-negative patients. Targeting both wild-type and mutant p53 in different subtypes of breast cancer has potential clinical relevance, and various therapeutic strategies including small molecule inhibitors, peptides, PROTACs, and genetic-based approaches are being developed. This review highlights the ongoing efforts to overcome p53 inactivation in breast tumors and discusses the efficacy and limitations of these therapeutic strategies.
Review
Biochemistry & Molecular Biology
Lucia Haronikova, Ondrej Bonczek, Pavlina Zatloukalova, Filip Kokas-Zavadil, Martina Kucerikova, Philip J. Coates, Robin Fahraeus, Borivoj Vojtesek
Summary: This review discusses the mechanism of action, determinants of sensitivity, and resistance issues of MDM2 inhibitors, emphasizing the need for patient stratification based on these aspects to achieve better clinical responses.
CELLULAR & MOLECULAR BIOLOGY LETTERS
(2021)
Article
Chemistry, Multidisciplinary
Seok-Beom Yong, Srinivas Ramishetti, Meir Goldsmith, Yael Diesendruck, Inbal Hazan-Halevy, Sushmita Chatterjee, Gonna Somu Naidu, Assaf Ezra, Dan Peer
Summary: Chemo-immunotherapy is an advanced therapeutic modality for cancer treatment, but many patients still respond poorly to it. This study developed a dual targeted HO1-inhibiting lipid nanotherapeutic that sensitizes cancer cells to chemotherapy and improves the responsiveness to immune checkpoint inhibitor therapy by reprogramming tumor myeloid cells.
ADVANCED MATERIALS
(2022)
Review
Pharmacology & Pharmacy
Chao Tang, Heng Liu, Yanpeng Fan, Jiahao He, Fuqiu Li, Jin Wang, Yuchuan Hou
Summary: Bladder cancer is commonly treated with transurethral resection followed by intravesical chemotherapy, but conventional methods lack selectivity and efficiency. Nanomedicines offer targeted drug delivery with improved efficacy and precision, overcoming the challenges of conventional treatments.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Dasom Kim, Dongwha Min, Joohee Kim, Min Jung Kim, Yerim Seo, Byung Hwa Jung, Seung-Hae Kwon, Hyunju Ro, Seoee Lee, Jason K. Sa, Ji-Yun Lee
Summary: In this study, nutlin-3a, an MDM2 antagonist, was found to inhibit the KRAS-PI3K/Akt-mTOR pathway and disrupt the fusion of autophagosomes and macropinosomes with lysosomes. This led to a non-apoptotic and catastrophic macropinocytosis-like cell death, which was dependent on GFPT2 of the hexosamine biosynthetic pathway in KRAS mutant/p53 wild type NSCLC cells.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Review
Oncology
Jin Wu, Guanting Lu, Xinjiang Wang
Summary: MDM4, originally named MDMX, is an oncogene that plays critical roles in promoting cancer cell growth and inhibiting apoptosis by blocking the p53 pathway. Different splicing isoforms of MDM4 show potential therapeutic value in cancer treatment, making them attractive targets for therapy.
AMERICAN JOURNAL OF CANCER RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Jiangsheng Xu, James G. Shamul, Elyahb Allie Kwizera, Xiaoming He
Summary: Mitochondria are critical organelles for producing energy in cells and can be targeted for cancer therapy. Mitochondria-targeting nanotechnologies have shown high efficacy for cancer treatment both in vitro and in vivo, and can be intelligently designed based on the characteristics of the tumor microenvironment.
Article
Chemistry, Multidisciplinary
Vasanthan Ravichandran, Quan Truong Hoang, Thuy Giang Nguyen Cao, Min Suk Shim
Summary: This study developed biodegradable PLGA nanocapsules encapsulating oxygen-deficient MnWOx nanoparticles (NPs) and doxorubicin (DOX) for cancer-targeted chemo-sonodynamic combination therapy. The results showed that these nanocapsules could generate singlet oxygen and hydroxyl radicals upon ultrasound stimulation, leading to increased intracellular ROS levels and sonodynamic effects, thus exhibiting efficient cytotoxicity against cancer cells.
JOURNAL OF INDUSTRIAL AND ENGINEERING CHEMISTRY
(2022)
Review
Pharmacology & Pharmacy
Anita Bakrania, Gang Zheng, Mamatha Bhat
Summary: This review highlights the progress, challenges, and targeting opportunities in HCC nanomedicine based on the growing literature in recent years. However, the translation of nanotheranostics in HCC is complicated by factors such as molecular heterogeneity and concomitant liver dysfunction.
Review
Pharmacology & Pharmacy
Pedro Cruz-Nova, Alejandra Ancira-Cortez, Guillermina Ferro-Flores, Blanca Ocampo-Garcia, Brenda Gibbens-Bandala
Summary: Nanoparticles have great potential in cancer treatment, as they can be combined with different molecules to improve therapeutic efficacy and reduce side effects. They can be used to enhance chemotherapy and radiation therapy, increase blood circulation time, and improve treatment outcomes through targeted delivery. Additionally, radiolabeled nanoparticles can be used for diagnosis, drug delivery, and photothermal therapy.
Article
Chemistry, Physical
Hakmin Mun, Yuriy Chaban, Tanveer A. Tabish, Nanasaheb Thorat, Nathan Cowieson, C. David Owen, Helen E. Townley
Summary: By functionalizing cubic phase nanocarriers, active tumor targeting towards rhabdomyosarcoma cells was achieved. The multi-functional nanoparticles showed a high cell uptake capacity and demonstrated potent anti-tumor effects.
Article
Chemistry, Physical
Hakmin Mun, Yuriy Chaban, Tanveer A. Tabish, Nanasaheb Thorat, Nathan Cowieson, C. David Owen, Helen E. Townley
Summary: This study evaluated a targeted nanoparticle system for rhabdomyosarcoma cells and found that the functionalized cubosomes had higher uptake rates in RMS cells and could bind to cells through electrostatic attraction and reaction coupling. Moreover, these functionalized nanoparticles exhibited high cytotoxicity against RMS cells.
