Review
Pharmacology & Pharmacy
Yue Li, Long Zhao, Xiao-Feng Li
Summary: Hypoxia is a key feature of most solid tumors, making them resistant to radiation and chemotherapy, but can be targeted with hypoxia-activated prodrugs. TH-302, a well-studied HAP, shows promising efficacy in preclinical and clinical studies, suggesting potential for future research directions.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Oncology
Hiroki Yamazaki, Seio Onoyama, Shunichi Gotani, Tatsuya Deguchi, Masahiro Tamura, Hiroshi Ohta, Hidetomo Iwano, Hidetaka Nishida, Peter J. Dickinson, Hideo Akiyoshi
Summary: This study investigated the effects of evofosfamide (EVO) on glycolytic metabolism in canine glioma (GL) cell lines with activated hypoxia-inducible factor 1 alpha (HIF-1 alpha). The results showed that EVO inhibited glycolytic metabolism and decreased tumor development in both in vitro and in vivo experiments. These findings suggest that EVO has potential as a therapeutic option for improving cancer metabolism in GL.
Article
Oncology
Enrique Grande, Cristina Rodriguez-Antona, Carlos Lopez, Teresa Alonso-Gordoa, Marta Benavent, Jaume Capdevila, Alex Teule, Ana Custodio, Isabel Sevilla, Jorge Hernando, Pablo Gajate, Javier Molina-Cerrillo, Juan Jose Diez, Maria Santos, Javier Lanillos, Rocio Garcia-Carbonero
Summary: The combination of Sunitinib and Evofosfamide showed moderate efficacy in pancreatic neuroendocrine tumors, with a median objective response rate of 17.6% and median progression-free survival of 10.4 months. However, treatment response did not correlate with analyzed biomarkers. The high systemic toxicity makes this therapeutic approach unfeasible and highlights the need for further research to overcome resistance to antiangiogenic agents in panNETs.
Article
Biochemistry & Molecular Biology
Shun Kishimoto, Jeffrey R. Brender, Gadisetti V. R. Chandramouli, Yu Saida, Kazutoshi Yamamoto, James B. Mitchell, Murali C. Krishna
Summary: The study demonstrates that evofosfamide not only kills the hypoxic regions in tumors, but also improves oxygenation in remaining tumor regions, providing a rationale for combination therapies with radiation and antiproliferatives. Monitoring changes in pO(2) following treatment may offer insight into treatment response.
ANTIOXIDANTS & REDOX SIGNALING
(2021)
Article
Pharmacology & Pharmacy
Vidhi M. Shah, Craig Dorrell, Adel Al-Fatease, Brittany L. Allen-Petersen, Yeonhee Woo, Yuliya Bortnyak, Rohi Gheewala, Brett C. Sheppard, Rosalie C. Sears, Adam Wg Alani
Summary: CPD100Li, a hypoxia-activated prodrug, demonstrates high efficacy in PDAC treatment with selective activation under low oxygen levels, improved cell inhibition and penetration in 3D spheroids and patient-derived organoids.
Article
Chemistry, Inorganic & Nuclear
Savyo S. Santana, Mauricio Lanznaster
Summary: Cobalt(III) complexes have been synthesized and studied for their potential use in delivering bioactive molecules to hypoxic regions of solid tumors. The donor/acceptor capabilities of the ancillary ligands play a role in the properties and reactivity of these complexes. The complexes show a suitable redox potential for biological conditions and exhibit O2-dependent dissociation of mesalazine.
INORGANIC CHEMISTRY COMMUNICATIONS
(2023)
Article
Nanoscience & Nanotechnology
De-Chao Yang, Lin-Feng Wen, Liyang Du, Cheng-Miao Luo, Zi-Yao Lu, Jian-Yong Liu, Zhonghui Lin
Summary: In this study, a multifunctional therapeutic BAC prodrug was designed and synthesized, which connected the chemotherapeutic drug and the fluorescent photothermal agent. The prodrug showed excellent biosafety and could perform chemotherapy in hypoxic cancer cells. Additionally, it could achieve irreversible cancer cell death through oxygen-independent photothermal therapy.
ACS APPLIED MATERIALS & INTERFACES
(2022)
Article
Materials Science, Biomaterials
Beibei Zhang, Rui Xue, Jisheng Lyu, An Gao, Chunyang Sun
Summary: External X-ray-induced photodynamic therapy (X-PDT) is a highly promising approach for combined cancer therapy, but it faces challenges such as low efficiency of photosensitizer delivery and radiation/drug resistance of hypoxic cells. In this study, an intelligent nanosized platform was developed for precise and synchronous X-PDT and selective hypoxia-motivated chemotherapy. The platform showed enhanced targeting ability in the tumor microenvironment, and the combination of X-PDT and hypoxia-motivated chemotherapy resulted in effective tumor cell death.
JOURNAL OF MATERIALS CHEMISTRY B
(2022)
Article
Chemistry, Multidisciplinary
Huisi Zhao, Zhengwei Liu, Yue Wei, Lu Zhang, Zhao Wang, Jinsong Ren, Xiaogang Qu
Summary: In this study, a NIR-II light promoted integrated catalyst is designed to accelerate the reaction efficiency and achieve a dual bioorthogonal reaction for combination therapy. The results show that this integrated catalyst exhibits significant anti-tumor activity in vivo.
Review
Chemistry, Medicinal
Emilie Anduran, Ludwig L. Dubois, Philippe Lambin, Jean-Yves Winum
Summary: The hypoxic tumor microenvironment presents a persistent challenge in solid tumor treatment. Efforts have been made to develop hypoxia-activated prodrugs (HAPs) of chemotherapeutic compounds to treat hypoxic tumors, but no HAP anti-cancer agent has been commercialized due to the lack of patient stratification based on reliable biomarkers predictive of a positive response to hypoxia-targeted therapy.
EXPERT OPINION ON THERAPEUTIC PATENTS
(2022)
Article
Chemistry, Multidisciplinary
Taslim A. Al-Hilal, Mohammad Anwar Hossain, Ahmed Alobaida, Farzana Alam, Ali Keshavarz, Eva Nozik-Grayck, Kurt R. Stenmark, Nadezhda A. German, Fakhrul Ahsan
Summary: The study developed a hypoxia-activated prodrug of fasudil that selectively suppresses ROCK activity under hypoxic conditions, exhibiting antiproliferative effects on disease-afflicted pulmonary arterial smooth muscle cells and pulmonary arterial endothelial cells. The prodrug has a long plasma half-life and does not affect systemic blood pressure.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Oncology
Elise Maubert, Valerie Weber, Aurelien Voissiere, Yvain Gerard, Veronique Dedieu, Francoise Degoul, Jean-Michel Chezal, Emmanuel Chautard, Elisabeth Miot-Noirault
Summary: This study demonstrated the potential interest of combining HAP ICF05016 with EBR for the management of EMC. The strategy enhanced EBR efficacy at a lower dose and improved survival without side effects, showing promising results in preclinical studies.
INVESTIGATIONAL NEW DRUGS
(2021)
Article
Chemistry, Multidisciplinary
Zhaoyu Ma, Yifan Zhang, Xinxin Dai, Weiyun Zhang, Mohamed F. Foda, Jin Zhang, Yanli Zhao, Heyou Han
Summary: The study presents a strategy of using selective tumor thrombus inducing hypoxia activation therapy to improve the therapeutic index of coagulation-based tumor therapy, which selectively activates thrombosis and increases hypoxia levels for enhanced treatment outcomes.
ADVANCED MATERIALS
(2021)
Article
Oncology
Aparna Hegde, Priyamvada Jayaprakash, Coline A. Couillault, Sarina Piha-Paul, Daniel Karp, Jordi Rodon, Shubham Pant, Siqing Fu, Ecaterina E. Dumbrava, Timothy A. Yap, Vivek Subbiah, Priya Bhosale, Cristian Coarfa, Jack P. Higgins, Eric T. Williams, Thomas F. Wilson, JoAnn Lim, Funda Meric-Bernstam, Elizabeth Sumner, Hira Zain, Di Nguyen, Ly M. Nguyen, Kimal Rajapakshe, Michael A. Curran, David S. Hong
Summary: The study investigated the combination of hypoxia-alleviating drug evofosfamide with immune checkpoint inhibitor ipilimumab for the treatment of cancers. Results showed partial responses in some patients, with preexisting immune gene signatures predicting treatment response and hypermetabolic tumors predicting disease progression.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Ala Yaromina, Lydia Koi, Lesley Schuitmaker, Alexander Marie-Madeleine Adrianus van der Wiel, Ludwig Jerome Dubois, Mechthild Krause, Philippe Lambin
Summary: A study shows that the novel hypoxia-activated prodrug CP-506 selectively targets hypoxic tumor cells and enhances the outcome of radiotherapy. The combination of CP-506 with radiation therapy is particularly effective for hypoxic tumors.
RADIOTHERAPY AND ONCOLOGY
(2023)
Review
Oncology
Jarlath C. Bolger, Claire L. Donohoe, Maeve Lowery, John V. Reynolds
Summary: The incidence of oesophageal cancer, particularly adenocarcinoma, has increased in the past four decades, with higher mortality rates. However, overall survival has doubled in the last 20 years, with advancements in early diagnosis and treatments. Endotherapy, surgical approaches, and new combination therapies have shown promise, along with targeted therapies and immunotherapy based on genomics and molecular biology advancements. This review focuses on curative intent treatments and highlights emerging advances.
BRITISH JOURNAL OF CANCER
(2022)
Article
Medicine, General & Internal
Fergus Keane, Megan Greally, Anne Horgan, Karen Duffy, Maeve Lowery, Petra Martin, Liam Grogan, Nemer Osman, Derek G. Power, Saira Nasim, Eileen M. O'Reilly, Gregory Leonard
Summary: Improvements in early cancer detection, screening, and treatment have led to an increase in cancer survivors globally, including in Ireland. However, there is a need for standardization in the surveillance of survivors of gastrointestinal malignancies in Ireland. A consensus group of Irish oncologists recommended adopting NCCN guidelines while individualizing care for each patient, with the hope of homogenizing survivorship practices and supporting survivorship initiatives by the NCCP.
IRISH JOURNAL OF MEDICAL SCIENCE
(2023)
Article
Medicine, General & Internal
Ruth Kieran, Carolyn Moloney, Scheryll Alken, Lynda Corrigan, David Gallagher, Cliona Grant, Fergal Kelleher, M. John Kennedy, Maeve A. Lowery, Michael McCarthy, Dearbhaile M. O'Donnell, Sue Sukor, Sinead Cuffe
Summary: This study investigated the knowledge of COVID among oncology patients and its impact on their behaviors, concerns, and healthcare experience. The results showed that despite education, some patients' recognition of COVID symptoms and preventive strategies was not optimal. COVID has been a significant stressor for patients, highlighting the need for more practical, financial, and psychological support.
IRISH JOURNAL OF MEDICAL SCIENCE
(2023)
Review
Gastroenterology & Hepatology
Emily Harrold, Lynda Corrigan, Simon Barry, Maeve Lowery
Summary: MET, the hepatocyte growth factor receptor, is amplified in 8% of gastroesophageal malignancies and associated with poor prognosis. However, targeting MET amplification and mutations has not yet significantly improved treatment outcomes for unselected GOC. Establishing a standardized definition of MET positivity is crucial for improving patient selection and successful clinical development of METi agents in GOC.
EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Anh Phong Tran, Christopher J. Tralie, Jose Reyes, Caroline Moosmuller, Zehor Belkhatir, Ioannis G. Kevrekidis, Arnold J. Levine, Joseph O. Deasy, Allen R. Tannenbaum
Summary: In this study, the time evolution of p21 and p53 in retinal pigment epithelial cells exposed to different levels of radiation was analyzed to investigate the effect of radiation on cell cycle arrest. Results showed that p21 levels, along with p53 levels to a lesser extent, had an impact on cell cycle arrest and the frequency of mitosis events.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Oncology
Dylan G. Hsu, Ase Ballangrud, Kayla Prezelski, Nathaniel C. Swinburne, Robert Young, Kathryn Beal, Joseph O. Deasy, Laura Cervino, Michalis Aristophanous
Summary: This study developed the METRO process to automatically process patient data and track brain metastases (BMs). Using a deep learning model, detections and volumetric measurements of BMs were obtained from longitudinal imaging. The accuracy of BM tracking was validated by comparing results with manual measurements and radiologists' assessments of new BMs.
PHYSICS & IMAGING IN RADIATION ONCOLOGY
(2023)
Meeting Abstract
Oncology
Corey Weistuch, Kevin Murgas, Ken Dill, Larry Norton, Joseph Deasy, Allen Tannenbaum
Meeting Abstract
Oncology
Jiening Zhu, Jung Hun Oh, Anish K. Simhal, Rena Elkin, Larry Norton, Joseph O. Deasy, Allen R. Tannenbaum
Meeting Abstract
Oncology
Anish K. Simhal, Kylee H. Maclachlan, Rena Elkin, Jiening Zhu, Saad Z. Usmani, Jonathan J. Keats, Larry Norton, Joseph O. Deasy, Jung Hun Oh, Allen Tannenbaum
Meeting Abstract
Oncology
Kevin A. Murgas, Jung H. Oh, Joseph O. Deasy, Allen R. Tannenbaum
Meeting Abstract
Oncology
Rena Elkin, Jung Hun Oh, Filemon Dela Cruz, Larry Norton, Joseph O. Deasy, Andrew L. Kung, Allen R. Tannenbaum
Article
Oncology
Z. A. R. Gouw, J. Jeong, A. Rimner, N. Y. Lee, A. Jackson, A. Fu, J-j. Sonke, J. O. Deasy
Summary: This study investigates the effectiveness of non-uniform fractionation schedules in radiotherapy for early-stage non-small cell lung cancer. Through modeling, optimized schedules are proposed to minimize local failures and toxicity risk. The results suggest that non-standard primer shot fractionation can reduce hypoxia-induced radioresistance and improve treatment outcomes.
RADIOTHERAPY AND ONCOLOGY
(2024)
Article
Oncology
Gerard M. Walls, Valentina Giacometti, Aditya Apte, Maria Thor, Conor McCann, Gerard G. Hanna, John 'Connor, Joseph O. Deasy, Alan R. Hounsell, Karl T. Butterworth, Aidan J. Cole, Suneil Jain, Conor K. McGarry
Summary: The study evaluated the performance of a deep learning-based cardiac substructure auto-segmentation tool on four-dimensional CT scans, showing good geometric and dosimetric agreement with manual segmentation and potential for clinical use.
PHYSICS & IMAGING IN RADIATION ONCOLOGY
(2022)
Article
Biochemical Research Methods
Maryam Pouryahya, Jung Hun Oh, Pedram Javanmard, James C. Mathews, Zehor Belkhatir, Joseph O. Deasy, Allen R. Tannenbaum
Summary: In this study, a novel network-based multiomics clustering method called aWCluster is proposed. By accentuating the genes that have concordant multiomics measurements in their interaction network, aWCluster successfully clusters different cancer types into classes with significantly different survival rates.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2022)
Article
Management
Masoud Zarepisheh, Linda Hong, Ying Zhou, Qijie Huang, Jie Yang, Gourav Jhanwar, Hai D. Pham, Pinar Dursun, Pengpeng Zhang, Margie A. Hunt, Gig S. Mageras, Jonathan T. Yang, Yoshiya (Josh) Yamada, Joseph O. Deasy
Summary: Radiotherapy treatment planning plays a crucial role in cancer treatment, but it is a time-consuming process that requires manual tuning of parameters. The advanced optimization tools developed by Memorial Sloan Kettering Cancer Center greatly improve the quality and speed of radiotherapy treatment planning, benefiting thousands of patients.
INFORMS JOURNAL ON APPLIED ANALYTICS
(2022)
Article
Oncology
Xiaofan Pu, Chaolei Zhang, Guoping Ding, Hongpeng Gu, Yang Lv, Tao Shen, Tianshu Pang, Liping Cao, Shengnan Jia
Summary: This study demonstrated the potential utility of the sEV-miRNA d-signature in the diagnosis of PDAC via machine learning methods. A novel sEV biomarker, miR-664a-3p, was identified for the diagnosis of PDAC. It can also potentially promote angiogenesis and metastasis, provide insight into PDAC pathogenesis, and reveal novel regulators of this disease.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Jiaping Wang, Zhijuan Xu, Yanli Lai, Yanli Zhang, Ping Zhang, Qitian Mu, Shujun Yang, Yongcheng Sun, Lixia Sheng, Guifang Ouyang
Summary: This study demonstrates the significance of PD-1 in EBV-infected lymphoma cells. Silencing PD-1 enhances the tumor targeting effect of EBV-specific killer T cells on B lymphocytes and attenuates the immune escape effect.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Qiliang Peng, Jialong Tao, Yingjie Xu, Yi Shen, Yong Wang, Yang Jiao, Yiheng Mao, Yaqun Zhu, Yulong Liu, Ye Tian
Summary: This study investigates the potential role of lipid metabolism-associated genes (LMAGs) in neoadjuvant chemoradiotherapy (nCRT) and immunotherapy for rectal cancer. The results suggest that the SREBF2 gene is a highly predictive factor for nCRT in rectal cancer and is associated with favorable prognosis. SREBF2 is also closely associated with immune cell infiltration and immunotherapy-related genes.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Shiquan Li, Nan Zhang, Yongping Yang, Tongjun Liu
Summary: This study investigated the potential molecular mechanism of SPDEF in immune evasion of colorectal cancer (CRC) and found that it suppresses immune evasion by activating CCL28 through the modulation of M2 polarization of macrophages. These findings provide a new research direction and potential therapeutic target for immunotherapy in CRC.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Manas Sehgal, Soundharya Ramu, Joel Markus Vaz, Yogheshwer Raja Ganapathy, Srinath Muralidharan, Sankalpa Venkatraghavan, Mohit Kumar Jolly
Summary: This study investigates the relationship between gene expression patterns and phenotypic plasticity and heterogeneity in colorectal cancer (CRC). The results demonstrate the interconnectedness between different Consensus Molecular Subtypes (CMS) of CRC and specific phenotypes such as epithelial and mesenchymal characteristics. Additionally, the study reveals correlations between metabolic pathways and phenotypic scores, as well as between PD-L1 activity and mesenchymal phenotype. Single-cell RNA sequencing analysis further confirms the heterogeneity of different CMS subtypes. These findings have important implications for understanding CRC heterogeneity and developing targeted therapies.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Yutong Zou, Siyao Guo, Yan Liao, Weidong Chen, Ziyun Chen, Junkai Chen, Lili Wen, Xianbiao Xie
Summary: This study found that ceramide metabolism is associated with the progression and clinical outcome of osteosarcoma by analyzing data from osteosarcoma patients. The gene ST3GAL1 plays an important role in osteosarcoma, regulating the tumor immune microenvironment and affecting T cell function. It may become a new target for the treatment of osteosarcoma.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Chuanhui Chen, Mengzhi Wan, Xiong Peng, Qing Zhang, Yu Liu
Summary: This study examines the function and mechanism of the ceRNA network centered around GPR37 in LUAD. The findings show that high expression of GPR37 in LUAD tissue samples is associated with poor prognosis, and it may regulate the expression of downstream target genes by competitively binding to lncRNA DLEU1 and miR-4458.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Junping Li, Hong Hu, Jinping He, Yuling Hu, Manting Liu, Bihui Cao, Dongni Chen, Xiaodie Ye, Jian Zhang, Zhiru Zhang, Wen Long, Hui Lian, Deji Chen, Likun Chen, Lili Yang, Zhenfeng Zhang
Summary: Sequential administration of CDC7 inhibitor XL413 after carboplatin enhances the chemotherapeutic effect of carboplatin on ovarian cancer cells, possibly by inhibiting homologous recombination repair activity and increasing the accumulation of chemotherapy-induced DNA damage.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Madison Catalanotto, Joel Markus Vaz, Camille Abshire, Reneau Youngblood, Min Chu, Herbert Levine, Mohit Kumar Jolly, Ana -Maria Dragoi
Summary: The study demonstrates that loss of FLASH in cancer cells leads to a hybrid E/M phenotype with high epithelial scores, suggesting FLASH acts as a repressor of the epithelial phenotype. Additionally, FLASH expression is inversely correlated with the epithelial score and subsets of mesenchymal markers are distinctly up-regulated in FLASH, NPAT, or SLBP-depleted cells.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Xiaorui Wang, Na Li, Minying Zheng, Yongjun Yu, Shiwu Zhang
Summary: Adipocytes are derived from pluripotent mesenchymal stem cells and histone modifications play a key role in their differentiation. Recent studies have shown that cancer stem cells can differentiate into adipocytes, reducing the malignancy of cancer cells.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Hana Q. Sadida, Alanoud Abdulla, Sara Al Marzooqi, Sheema Hashem, Muzafar A. Macha, Ammira S. Al-Shabeeb Akil, Ajaz A. Bhat
Summary: Cancer heterogeneity and drug resistance are major obstacles to effective cancer treatment, and epigenetic modifications play a pivotal role in these processes. This review explores essential epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodeling, and discusses their complex contributions to cancer biology. However, the interplay of epigenetic and genetic changes in cancer cells presents unique challenges that must be addressed to fully exploit the potential of epigenetic modifications.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Pedro De Marchi, Leticia Ferro Leal, Luciane Sussuchi da Silva, Rodrigo de Oliveira Cavagna, Flavio Augusto Ferreira da Silva, Vinicius Duval da Silva, Eduardo C. A. da Silva, Augusto O. Saito, Vladmir C. Cordeiro de Lima, Rui Manuel Reis
Summary: The TIS and IFN-gamma signatures are predictive biomarkers for identifying NSCLC patients who could potentially benefit from immune checkpoint inhibitor therapies.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Giovanni Marchi, Anna Rajavuori, Mai T. N. Nguyen, Kaisa Huhtinen, Sinikka Oksa, Sakari Hietanen, Sampsa Hautaniemi, Johanna Hynninen, Jaana Oikkonen
Summary: The study shows that ctDNA can adequately represent high-grade serous ovarian carcinoma (HGSC), and the mutations observed at relapse suggest personalized therapy options.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Yuncang Yuan, Jiawei Fan, Dandan Liang, Shijie Wang, Xu Luo, Yongjie Zhu, Nan Liu, Tingxiu Xiang, Xudong Zhao
Summary: This study demonstrates that csGRP78-directed CAR-T cells can selectively kill pancreatic cancer cells, and the combination with chemotherapy enhances cytotoxicity.
TRANSLATIONAL ONCOLOGY
(2024)
Article
Oncology
Niyati Piplani, Tanusri Roy, Neha Saxena, Shamik Sen
Summary: The glycocalyx, a protective barrier surrounding cells, has been found to play a role in cancer cell proliferation, survival, and metastasis. However, its function in maintaining DNA/nuclear integrity during migration through dense matrices has not been explored. This study shows that the bulkiness of the glycocalyx is inversely associated with nuclear stresses, and highlights its mechanical role in shielding migration-associated stresses.
TRANSLATIONAL ONCOLOGY
(2024)