Article
Multidisciplinary Sciences
Tom Egger, Benoit Bordignon, Arnaud Coquelle
Summary: Colorectal cancer is a common malignancy and its therapy often causes replication stress. The ATR-CHK1 pathway is responsible for managing this stress, and mutations in the ATR gene can increase sensitivity to drugs and enhance their synergy. These mutations lead to DNA damage, but targeting RPA and DNA-PK can optimize inhibition of the ATR-CHK1 pathway.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Monika K. Prelowska, Dawid Mehlich, M. Talha Ugurlu, Hanna Kedzierska, Aleksandra Cwiek, Artur Kosnik, Klaudia Kaminska, Anna A. Marusiak, Dominika Nowis
Summary: The combination of ASCT2 inhibitor and proteasome inhibitor enhances cytotoxic activity through inducing apoptosis and modulating autophagy.
Article
Multidisciplinary Sciences
Yiji Liao, Chen-Hao Chen, Tengfei Xiao, Barbara de la Pena Avalos, Eloise Dray, Changmeng Cai, Shuai Gao, Neel Shah, Zhao Zhang, Avery Feit, Pengya Xue, Zhijie Liu, Mei Yang, Ji Hoon Lee, Han Xu, Wei Li, Shenglin Mei, Roodolph S. Pierre, Shaokun Shu, Teng Fei, Melissa Duarte, Jin Zhao, James E. Bradner, Kornelia Polyak, Philip W. Kantoff, Henry Long, Steven P. Balk, X. Shirley Liu, Myles Brown, Kexin Xu
Summary: Drugs that block the activity of the methyltransferase EZH2 have shown potential for treating non-Hodgkin lymphomas with EZH2 gain-of-function mutations. This study reveals that EZH2 inhibitors can also inhibit the growth of castration-resistant prostate cancer (CRPC) cells by blocking the transactivation activity of EZH2 and down-regulating DNA damage repair (DDR) genes. The expression of DDR genes is correlated with EZH2 dependency and cellular sensitivity to EZH2 inhibitors in various types of solid tumors. These findings provide insights into the mechanism of action of EZH2 inhibitors and have implications for combination cancer therapies.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Immunology
Colin G. Graydon, Shifa Mohideen, Keith R. Fowke
Summary: This review outlines the importance of LAG3 as an immune checkpoint in cancer, infectious diseases, and autoimmunity, while also highlighting the gaps in understanding its biology, regulation, and mechanisms of action. Further research is needed to fully elucidate the role of LAG3 in disease and explore its potential as a target for therapeutic interventions.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Jie Zhou, Run-Cong Nie, Zhang-Ping He, Xiao-Xia Cai, Jie-Wei Chen, Wen-ping Lin, Yi-Xin Yin, Zhi-Cheng Xiang, Tian-Chen Zhu, Juan-Juan Xie, You-Cheng Zhang, Xin Wang, Peng Lin, Dan Xie, Alan D. D'Andrea, Mu-Yan Cai
Summary: This study reveals the important role of STAG2 in DNA repair and its potential therapeutic implications. STAG2 deficiency leads to increased DNA double-strand breaks and enhances the sensitivity of cancer cells to ATM inhibitors. Additionally, a synthetic lethality relationship between ATM and STAG2 is uncovered, providing insights for the development of treatment strategies for STAG2-mutant tumors.
Article
Oncology
Simone Punt, Shruti Malu, Jodi A. McKenzie, Soraya Zorro Manrique, Elien M. Doorduijn, Rina M. Mbofung, Leila Williams, Deborah A. Silverman, Emily L. Ashkin, Ana Lucia Dominguez, Zhe Wang, Jie Qing Chen, Sourindra N. Maiti, Trang N. Tieu, Chengwen Liu, Chunyu Xu, Marie-Andree Forget, Cara Haymaker, Jahan S. Khalili, Nikunj Satani, Florian Muller, Laurence J. N. Cooper, Willem W. Overwijk, Rodabe N. Amaria, Chantale Bernatchez, Timothy P. Heffernan, Weiyi Peng, Jason Roszik, Patrick Hwu
Summary: This study identified Aurora kinase as a mediator of melanoma cell resistance to T-cell-mediated cytotoxicity and found that Aurora kinase inhibitors synergize with T-cell-mediated cytotoxicity in vitro, potentially enhancing antitumor immunity in vivo. However, the response of Aurora kinase inhibition in combination with immunotherapy in vivo varied, indicating its activity is influenced by other factors in the tumor microenvironment. Further research is needed to determine the primary resistance mechanism to this therapeutic intervention.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Biology
A. Jane Bardwell, Beibei Wu, Kavita Y. Sarin, Marian L. Waterman, Scott X. Atwood, Lee Bardwell
Summary: There is crosstalk between the Hedgehog and MAPK signaling pathways in cancer, leading to resistance to Hedgehog pathway inhibitors. The study demonstrates that MAP kinase-mediated phosphorylation weakens the binding of the GLI1 transcription factor to its negative regulator SUFU. The phosphorylation of GLI1 at three specific target sites decreases the affinity of GLI1-SUFU binding, and this effect is not observed when only one or two sites are phosphorylated.
LIFE SCIENCE ALLIANCE
(2022)
Article
Biochemistry & Molecular Biology
Nader El-Sayes, Alyssa Vito, Omar Salem, Samuel Tekeste Workenhe, Yonghong Wan, Karen Mossman
Summary: This study demonstrates that the sensitivity of dMMR CRC to immune checkpoint therapy can be improved by combining low-dose chemotherapy and oncolytic HSV-1. This combination treatment promotes immune cell infiltration into the tumor and enhances therapeutic efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Yousef R. Badran, Fangwen Zou, Sienna M. Durbin, Barbara E. Dutra, Hamzah Abu-Sbeih, Anusha S. Thomas, Mehmet Altan, John A. Thompson, Wei Qiao, Donna E. Leet, Po-Ying Lai, Nora K. Horick, Michael A. Postow, David M. Faleck, Yinghong Wang, Michael Dougan
Summary: This study examined the effects of resuming immune checkpoint inhibitor (ICI) therapy with or without concurrent selective immunosuppressive therapy (SIT) in patients with immune-related enterocolitis (irEC). The results showed that after resolution of irEC symptoms, reinitiation of ICI with concurrent SIT was safe, reduced the risk of severe irEC recurrence, and did not negatively impact survival outcomes.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2023)
Article
Biochemistry & Molecular Biology
Kolin M. Clark, Josh G. Kim, Qiankun Wang, Hongbo Gao, Rachel M. Presti, Liang Shan
Summary: The sensitization of the CARD8 inflammasome to non-nucleoside reverse transcriptase inhibitors (NNRTIs) can be achieved through chemical inhibition of the negative regulator DPP9. The DPP9 inhibitor Val-boroPro (VbP) can kill HIV-1-infected cells without NNRTIs and synergize with NNRTIs to promote clearance of infected cells. This offers a promising strategy for enhancing NNRTI efficacy in eliminating HIV-1 reservoirs.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Pranavi Koppula, Kellen Olszewski, Yilei Zhang, Lavanya Kondiparthi, Xiaoguang Liu, Guang Lei, Molina Das, Bingliang Fang, Masha Poyurovsky, Boyi Gan
Summary: KEAP1 deficiency in lung cancer cells increases glucose dependency, making them more vulnerable to glucose deprivation. This study reveals a potential therapeutic target by targeting metabolic vulnerabilities in KEAP1-mutant lung cancer.
Article
Biochemistry & Molecular Biology
Yuka Ishihara, Kiyoshiro Nakamura, Shunsuke Nakagawa, Yasuhiro Okamoto, Masatatsu Yamamoto, Tatsuhiko Furukawa, Kohichi Kawahara
Summary: The nucleolar stress response, activated by the perturbation of ribosome biogenesis, can suppress tumor progression through the activation of the p53 pathway. This study investigated whether topoisomerase inhibitors can induce the nucleolar stress response and found that the sensitivity of cancer cells to these inhibitors is regulated by the nucleolar protein L11. The expression of L11 can potentially serve as a predictor of the therapeutic efficacy of topoisomerase inhibitors and enhance their effectiveness.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Yang Liu, Lu Wang, Xin Xu, Yue Yuan, Bo Zhang, Zeyang Li, Yuchen Xie, Rui Yan, Zeqi Zheng, Jianguo Ji, Johanne M. Murray, Antony M. Carr, Daochun Kong
Summary: This study reveals the mechanism by which the checkpoint kinases Rad3ATR and Cds1Chk2 directly regulate the replicative helicase under replication stress. When replication forks stall, Cds1Chk2 phosphorylates Cdc45, reducing CMG helicase activity and preserving the integrity of stalled replisomes and replication forks.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Medicine, General & Internal
Niccolo Rossi, Karla A. Lee, Maria Bermudez, Alessia Visconti, Andrew Maltez Thomas, Laura A. Bolte, Johannes R. Bjork, Laura Kist de Ruijter, Julia Newton-Bishop, Mark Harland, Heather M. Shaw, Mark Harries, Joseph Sacco, Ruth Board, Paul Lorigan, Elisabeth G. E. de Vries, Nicola Segata, Leonie Taams, Sophie Papa, Tim D. Spector, Paul Nathan, Rinse K. Weersma, Geke A. P. Hospers, Rudolf S. N. Fehrmann, Veronique Bataille, Mario Falchi
Summary: This study investigates the potential of circulating inflammatory proteins as biomarkers for immune checkpoint inhibitor therapy in advanced melanoma. The findings suggest that pre-treatment levels of IL-6, HGF, and MCP-2 are associated with treatment response, while on-treatment changes in these proteins are not correlated with response. Inflammatory proteins could serve as predictive biomarkers of ICI response and potential targets for combination therapy.
Article
Medicine, General & Internal
Ritu Shrestha, Prashanth Prithviraj, Kim R. Bridle, Darrell H. G. Crawford, Aparna Jayachandran
Summary: Hepatocellular carcinoma (HCC) is a common malignancy, and treatment with Sorafenib may lead to drug resistance. Research shows that combining inhibition of EMT and immune checkpoint molecules can enhance the sensitivity of HCC cells to Sorafenib.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Ranganatha R. Somasagara, Kaushlendra Tripathi, Sebastian M. Spencer, David W. Clark, Reagan Barnett, Lavanya Bachaboina, Jennifer Scalici, Rodney P. Rocconi, Gary A. Piazza, Komaraiah Palle
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2016)
Article
Biochemistry & Molecular Biology
Kaushlendra Tripathi, Chinnadurai Mani, Ranganatha R. Somasagara, David W. Clark, Venkateshwari Ananthapur, Kambappa Vinaya, Komaraiah Palle
MOLECULAR CARCINOGENESIS
(2017)
Meeting Abstract
Oncology
Chinnadurai Mani, David Clark, Ranganatha Somasagara, Sebastian Spencer, Kaushlendra Tripathi, Komariah Palle
Article
Biochemistry & Molecular Biology
Kaushlendra Tripathi, Vishnu C. Ramani, Shyam K. Bandari, Rada Amin, Elizabeth E. Brown, Joseph P. Ritchie, Mark D. Stewart, Ralph D. Sanderson
Article
Biochemistry & Molecular Biology
Chinnadurai Mani, Kaushlendra Tripathi, Shan Luan, David W. Clark, Joel F. Andrews, Alessandro Vindigni, Gary Thomas, Komaraiah Palle
Review
Cell Biology
Sunil Rangarajan, Jillian R. Richter, Robert P. Richter, Shyam K. Bandari, Kaushlendra Tripathi, Israel Vlodavsky, Ralph D. Sanderson
JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY
(2020)
Article
Cell Biology
Rada Amin, Kaushlendra Tripathi, Ralph D. Sanderson
Article
Oncology
Chinnadurai Mani, Kaushlendra Tripathi, Sandeep Chaudhary, Ranganatha R. Somasagara, Rodney P. Rocconi, Chiquito Crasto, Mark Reedy, Mohammad Athar, Komaraiah Palle
Summary: Research has shown that inhibition of GLI1 in ovarian cancer cells can induce HR deficiency and replication stress in HR-proficient cells, and when used in combination with PARP inhibitors, it exhibits synergistic effects, enhancing cytotoxicity and DNA damage.
Article
Biochemistry & Molecular Biology
Chinnadurai Mani, Kaushlendra Tripathi, Tasmin R. Omy, Mark Reedy, Upender Manne, Komaraiah Palle
Summary: Inhibition of GLI1 in TNBC cells downregulates FANCD2 expression and induces HR deficiency, showing synergistic lethality when combined with a PARP inhibitor. This study provides a potential new approach for treating TNBC.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Ralph D. Sanderson, Shyam K. Bandari, Kaushlendra Tripathi
Meeting Abstract
Oncology
Sunil Rangarajan, Kaushlendra Tripathi, Shyam Kumar Bandari, Elizabeth E. Brown, Ralph D. Sanderson
JOURNAL OF CLINICAL ONCOLOGY
(2020)
Meeting Abstract
Oncology
Chinnadurai Mani, Kaushlendra Tripathi, David W. Clark, Gary Thomas, Komaraiah Palle
Article
Oncology
Shyam K. Bandari, Kaushlendra Tripathi, Sunil Rangarajan, Ralph D. Sanderson
Meeting Abstract
Oncology
Kaushlendra Tripathi, Chinnadurai Mani, David W. Clark, Komaraiah Palle
CLINICAL CANCER RESEARCH
(2019)
Meeting Abstract
Biochemistry & Molecular Biology
Komaraiah Palle, Kaushlendra Tripathi, David W. Clark, Chinnadurai Mani