Article
Biochemistry & Molecular Biology
Fabiola N. Velazquez, Jeffrey L. Stith, Leiqing Zhang, Amira M. Allam, John Haley, Lina M. Obeid, Ashley J. Snider, Yusuf A. Hannun
Summary: This study suggests that targeting sphingosine kinase 1 (SK1), a key enzyme upregulated in various types of cancer, can effectively decrease tumor growth in lymphoma without functional p53. This positions SK1 as a potential therapeutic target for tumors that lack functional p53.
Article
Oncology
Suchitra Mohanty, Amit Kumar, Piyanki Das, Sushil Kumar Sahu, Ratnadeep Mukherjee, Rajagopal Ramachandranpillai, Santhosh Sankaran Nair, Tathagata Choudhuri
Summary: This study demonstrates that downregulation of Nm23-H1 expression in KSHV-infected primary effusion lymphoma (PEL) cells and its overexpression trigger apoptosis by impairing vFLIP K13-driven NF-kappa B signaling. These findings suggest the therapeutic implications of Nm23-H1 for primary effusion lymphomas.
Article
Virology
Daniel Dunham, Prasanth Viswanathan, Jackson Gill, Mark Manzano
Summary: Kaposi's sarcoma-associated herpesvirus (KSHV) causes primary effusion lymphoma (PEL) and PEL cell lines show addiction to MCL1 for survival. MCL1 functions mainly to prevent BAX/BAK1-mediated apoptosis in PEL cells, and its selective requirement is due to its excess expression over the BCL2 family.
JOURNAL OF VIROLOGY
(2022)
Review
Oncology
Saida Mebarek, Najwa Skafi, Leyre Brizuela
Summary: Prostate cancer is the second most common cancer in men worldwide, with the majority of patients being above 65. Sphingosine 1-phosphate (S1P) is a bioactive lipid that plays a crucial role in the oncogenesis of prostate cancer. S1P metabolism and its enzymes have been extensively studied in relation to prostate cancer development and potential therapeutic targets. This review summarizes the significant findings and the current progress in targeting S1P metabolism for prostate cancer treatment.
Article
Cell Biology
Lu Jin, Jin Zhu, Linya Yao, Gang Shen, Bo-xin Xue, Wei Tao
Summary: This study found that SphK1 and SphK2 are upregulated in human prostate cancer tissues. The use of SKI-178 effectively inhibits the growth and migration of prostate cancer cells, exerting cytotoxic effects through the inhibition of SphK activity and induction of ceramide production.
CELL DEATH & DISEASE
(2023)
Review
Oncology
Preeti Gupta, Aaliya Taiyab, Afzal Hussain, Mohamed F. Alajmi, Asimul Islam, Md. Imtaiyaz Hassan
Summary: Cancer is a leading cause of global mortality, with SphK1 and its metabolite S1P being potential therapeutic targets due to their over-expression in various cancers and metabolic disorders. This review discusses the sphingolipid metabolism and the role of SphK isoforms in human malignancies, as well as the potential of SphK inhibitors in cancer therapy. It highlights the importance of sphingolipid metabolites in regulating physiological processes and the significance of the SphK/S1P signaling axis in human pathologies.
Article
Medicine, General & Internal
Hui-Ming Lin, Blossom Mak, Nicole Yeung, Kevin Huynh, Thomas G. Meikle, Natalie A. Mellett, Edmond M. Kwan, Heidi Fettke, Ben Tran, Ian D. Davis, Kate L. Mahon, Alison Zhang, Martin R. Stockler, Karen Briscoe, Gavin Marx, Megan Crumbaker, Phillip D. Stricker, Pan Du, Jianjun Yu, Shidong Jia, Tahlia Scheinberg, Michael Fitzpatrick, Paul Bonnitcha, David R. Sullivan, Anthony M. Joshua, Arun A. Azad, Lisa M. Butler, Peter J. Meikle, Lisa G. Horvath
Summary: This study focused on investigating the association of ceramide-sphingosine-1-phosphate signalling axis with ARSI resistance in mCRPC. Elevated circulating ceramide levels were found to be associated with shorter radiological progression-free survival and overall survival in men with mCRPC. Combining AR aberrations with elevated ceramide levels resulted in a worse prognosis, and SPHK inhibitors showed potential to enhance the efficacy of enzalutamide.
Article
Microbiology
Jungang Lan, Yeqing Wang, Shusheng Yue, Duo Xu, Yinan Li, Xiangyu Peng, Jiao Hu, Enguo Ju, Shanping He, Tingting Li
Summary: KSHV causes both latent and lytic infections, and PEL is a B-cell lymphoma that is predominantly latently infected by KSHV. Inhibiting FoxO proteins can induce KSHV lytic replication and result in massive cell death in PEL.
Article
Oncology
Aurelien Haustrate, George Shapovalov, Corentin Spriet, Clement Cordier, Artem Kondratskyi, Lucile Noyer, Francois Foulquier, Natalia Prevarskaya, V'yacheslav Lehen'kyi
Summary: The upregulation of TRPV6 channel in cancer is associated with poor prognosis, but there is no reliable tool to target it. Two antibodies have been generated that can bind to TRPV6 and transiently activate calcium currents. This activation leads to apoptosis induction in prostate cancer cells, with only cells lacking TRPV6 expression being able to avoid death. Therefore, activating the TRPV6 channel may be more prospective than inhibiting it.
Article
Biochemistry & Molecular Biology
Dorit Avni, Kuzhuvelil B. Harikumar, Arun J. Sanyal, Sarah Spiegel
Summary: In this study, the researchers found that deletion of SphK1 significantly decreased liver damage and mortality rate caused by acute liver failure, likely through regulating the secretion of pro-inflammatory cytokine TNF alpha. The findings suggest that SphK1 may play a crucial role in the development of acute liver failure and could be a potential therapeutic target for fulminant hepatitis.
Article
Cell Biology
Gonghong Yan, Augustin Luna, Heping Wang, Behnaz Bozorgui, Xubin Li, Maga Sanchez, Zeynep Dereli, Nermin Kahraman, Goknur Kara, Xiaohua Chen, Caishang Zheng, Daniel McGrail, Nidhi Sahni, Yiling Lu, Ozgun Babur, Murat Cokol, Bora Lim, Bulent Ozpolat, Chris Sander, Gordon B. Mills, Anil Korkut
Summary: This study suggests that targeting MCL1 and BET may have therapeutic potential for the treatment of basal-like breast cancers. BET inhibition induces an adaptive response leading to the evasion of apoptosis in breast cancer cells driven by MCL1 protein. The mechanism involves upregulation of lipid synthesis enzymes, which affects cell motility and membrane fluidity, as well as the activation of HER2/EGFR signaling. MCL1 copy-number alterations are associated with the effectiveness of BET and MCL1 co-targeting.
Article
Plant Sciences
Mikinori Ueno, Ryusho Kariya, Gunya Sittithumcharee, Seiji Okada
Summary: The study demonstrated that cucurbitacin B (CuB) can effectively inhibit cell proliferation and induce apoptosis in Primary Effusion Lymphoma (PEL) cells in a dose-dependent manner. CuB also has an impact on cell cycle arrest and affects signaling pathways related to KSHV-derived protein activation. In vivo experiments showed that CuB significantly inhibited solid tumor growth, indicating its potential as a promising agent for PEL treatment.
Article
Medicine, Research & Experimental
Thao M. Nguyen, Manasi Jambhrunkar, Sook S. Wong, David M. Ross, Paul Joyce, John W. Finnie, Jim Manavis, Kristen Bremmell, Melissa R. Pitman, Clive A. Prestidge
Summary: Liposome-based delivery system of MP-A08 enhances its potency against AML cells and significantly prolongs overall survival in mice with human AML disease, indicating its potential as a novel treatment for AML.
MOLECULAR PHARMACEUTICS
(2023)
Article
Oncology
Prabha Shrestha, Yana Astter, David A. Davis, Ting Zhou, Constance M. M. Yuan, Ramya Ramaswami, Hao-Wei Wang, Kathryn Lurain, Robert Yarchoan
Summary: Primary effusion lymphoma (PEL), caused by Kaposi sarcoma-associated herpesvirus (KSHV), is an aggressive non-Hodgkin lymphoma with no standard therapy. CD38 is highly expressed in PEL cells, and daratumumab (Dara) shows significant antibody-dependent cell-mediated cytotoxicity (ADCC) against PEL cells with high CD38 levels. Two FDA-approved drugs, all-trans-retinoic acid (ATRA) and pomalidomide (Pom), increase CD38 expression in low-CD38 expressing PEL cells, enhancing Dara-induced ADCC.
Article
Biochemistry & Molecular Biology
Sonam Roy, Shama Khan, Deeba Shamim Jairajpuri, Afzal Hussain, Mohamed F. Alajmi, Asimul Islam, Suaib Luqman, Suhel Parvez, Md Imtaiyaz Hassan
Summary: Sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate (S1P) signaling play crucial roles in regulating various diseases, especially in cancers such as breast, lung, colon, and hepatocellular carcinomas. Compounds like cinchonine and colcemid have high affinity for SphK1 and show potential in inhibiting its kinase activity.
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
(2022)
Article
Oncology
Gunjan Mandal, Subir Biswas, Carmen M. Anadon, Xiaoqing Yu, Chandler D. Gatenbee, Sandhya Prabhakaran, Kyle K. Payne, Ricardo A. Chaurio, Alexandra Martin, Patrick Innamarato, Carlos Moran, John J. Powers, Carly M. Harro, Jessica A. Mine, Kimberly B. Sprenger, Kristen E. Rigolizzo, Xuefeng Wang, Tyler J. Curiel, Paulo C. Rodriguez, Alexander R. Anderson, Ozlen Saglam, Jose R. Conejo-Garcia
Summary: This study reveals the crucial role of humoral immunity in human endometrial cancer and provides insights for the development of novel immunotherapies against this prevalent malignancy. Coordinated cellular and humoral immune responses, particularly involving B cells and IgA:plgR interactions, determine the progression of endometrial cancer and its response to treatment.
Article
Oncology
Julie A. Means-Powell, Ingrid A. Mayer, Roohi Ismail-Khan, Luis Del Valle, Debra Tonetti, Vandana G. Abramson, Melinda S. Sanders, Richard M. Lush, Claudia Sorrentino, Samarpan Majumder, Lucio Miele
Summary: A phase 1b trial of Notch inhibitor GSI RO4929097 with exemestane in 15 patients with ER+, metastatic breast cancer was conducted. The combination was well-tolerated, with clinical responses observed in a portion of the patients. The results suggest that further investigation should be done on combinations of Notch inhibitors and endocrine therapy in endocrine-refractory breast cancer.
CLINICAL BREAST CANCER
(2022)
Article
Immunology
Ricardo A. Chaurio, Carmen M. Anadon, Tara Lee Costich, Kyle K. Payne, Subir Biswas, Carly M. Harro, Carlos Moran, Antonio C. Ortiz, Carla Cortina, Kristen E. Rigolizzo, Kimberly B. Sprenger, Jessica A. Mine, Patrick Innamarato, Gunjan Mandal, John J. Powers, Alexandra Martin, Zhitao Wang, Sumit Mehta, Bradford A. Perez, Roger Li, John Robinson, Jodi L. Kroeger, Tyler J. Curiel, Xiaoqing Yu, Paulo C. Rodriguez, Jose R. Conejo-Garcia
Summary: Regulation of PD-1 expression on Tfh cells affects Tfh cell differentiation. Inhibiting SATB1 expression promotes Tfh cell differentiation and enhances immune responses. Transfer of Tfh cells can induce TLS formation and inhibit tumor growth.
Article
Oncology
Amrita Basu, Gabriella K. Albert, Sabrina Awshah, Jashodeep Datta, Krithika N. Kodumudi, Corey Gallen, Amber Beyer, Keiran S. M. Smalley, Paulo C. Rodriguez, Derek R. Duckett, Peter A. Forsyth, Aixa Soyano, Gary K. Koski, Ricardo Lima Barros Costa, Heather Han, Hatem Soliman, Marie Catherine Lee, Pawel Kalinski, Brian J. Czerniecki
Summary: This study identifies immunogenic MHC class II-binding HER3 peptides that elicit HER3-specific CD4(+) Th1 responses, suggesting their potential application in immunotherapies for HER3-overexpressing tumors.
CANCER IMMUNOLOGY RESEARCH
(2022)
Article
Biology
Alyssa Obermayer, Li Dong, Qianqian Hu, Michael Golden, Jerald D. D. Noble, Paulo Rodriguez, Timothy J. J. Robinson, Mingxiang Teng, Aik-Choon Tan, Timothy I. I. Shaw
Summary: This paper presents a R Shiny framework called DRPPM-EASY for integrative multi-omics analysis of cancer datasets. The framework provides a user-friendly interface for exploring and integrating various omics data, reducing the need for computational experience. By analyzing transcriptomic and proteomic data, the authors identified cancer cell proliferative features associated with USP7 gene knockout and disruption of protein degradation and spliceosome. Additionally, they developed an extension called DRPPM-EASY-CCLE with preloaded cancer cell line data for sample querying and phenotype assignment.
Article
Oncology
Jiannong Li, Inna Smalley, Zhihua Chen, Jheng-Yu Wu, Manali S. Phadke, Jamie K. Teer, Thanh Nguyen, Florian A. Karreth, John M. Koomen, Amod A. Sarnaik, Jonathan S. Zager, Nikhil I. Khushalani, Ahmad A. Tarhini, Vernon K. Sondak, Paulo C. Rodriguez, Jane L. Messina, Y. Ann Chen, Keiran S. M. Smalley
Summary: This study used single-cell RNA sequencing to analyze acral melanoma and found that it has a suppressed immune environment compared to non-acral cutaneous melanoma. Multiple therapeutically tractable immune checkpoints were observed in acral melanoma, offering new options for clinical translation.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
Vincent Law, Zhihua Chen, Francesca Vena, Inna Smalley, Robert Macaulay, Brittany R. Evernden, Nam Tran, Yolanda Pina, John Puskas, Gisela Caceres, Simon Bayle, Joseph Johnson, James K. C. Liu, Arnold Etame, Michael Vogelbaum, Paulo Rodriguez, Derek Duckett, Brian Czerniecki, Ann Chen, Keiran S. M. Smalley, Peter A. Forsyth
Summary: This study demonstrates that CSF-CTCs can be grown in vitro and in vivo from some melanoma patients with LMD and used as preclinical models. These models retained melanoma expression patterns and had signaling pathways that are therapeutically targetable.
Article
Oncology
Xiaofei Song, Shiun Chang, Lucia Seminario-Vidal, Alvaro de Mingo Pulido, Leticia Tordesillas, Xingzhi Song, Rhianna A. Reed, Andrea Harkins, Shannen Whiddon, Jonathan Nguyen, Carlos Moran Segura, Chaomei Zhang, Sean Yoder, Zena Sayegh, Yun Zhao, Jane L. Messina, Carly M. Harro, Xiaohui Zhang, Jose R. Conejo-Garcia, Anders Berglund, Lubomir Sokol, Jianhua Zhang, Paulo C. Rodriguez, James J. Mule, Andrew P. Futreal, Kenneth Y. Tsai, Pei-Ling Chen
Summary: This study comprehensively investigated the tumor ecosystem of transformed CTCL using multiomics approaches. The findings revealed high tumor mutation burden, recurrently mutated pathways, and immune escape related changes in tCTCL. In addition, pharmacologic perturbation targeting OXPHOS and MYC showed promising antitumor activities, and intercellular communications between malignant T cells and macrophages/B cells were identified.
Article
Medicine, General & Internal
Maria Dulfary Sanchez-Pino, William S. Richardson, Jovanny Zabaleta, Ramesh Thylur Puttalingaiah, Andrew G. Chapple, Jiao Liu, Yonghyan Kim, Michelle Ponder, Randi DeArmitt, Lyndsey Buckner Baiamonte, Dorota Wyczechowska, Liqin Zheng, Amir A. Al-Khami, Jone Garai, Rachel Martini, Melissa Davis, Jessica Koller Gorham, James B. Wooldridge, Paulo C. Rodriguez, Lucio Miele, Augusto C. Ochoa
Summary: The number of LDN in the circulation is increased in obese patients and is associated with an inflammatory gene signature. Bariatric surgery significantly reduces LDN levels and improves metabolic parameters.
Article
Oncology
Guanyi Zhang, Zemin Wang, Jasmin Bavarva, Katherine J. Kuhns, Jianhui Guo, Elisa M. Ledet, Chiping Qian, Yuan Lin, Zhide Fang, Jovanny Zabaleta, Luis Del Valle, Jennifer J. Hu, Diptasri Mandal, Wanguo Liu
Summary: This study has identified a rare ADPRHL1 gene mutation associated with prostate cancer in African American families. The mutation leads to abnormal cell proliferation and activation of the PARP1 pathway, increasing the response of prostate cancer cells to DNA damage and promoting tumor growth. ADPRHL1 acts as a tumor suppressor in normal prostate tissue. The findings of this study provide a potential strategy for ADPRHL1 mutation detection in prostate cancer-risk assessment and a potential therapeutic application for individuals with prostate cancer in African American families.
MOLECULAR CANCER RESEARCH
(2022)
Editorial Material
Oncology
Mauro Tognon, George A. Calin, Luis Del Valle
FRONTIERS IN ONCOLOGY
(2022)
Review
Cell Biology
Zaid Khreefa, Mallory T. T. Barbier, Ali Riza Koksal, Gordon Love, Luis Del Valle
Summary: The novel coronavirus, SARS-CoV-2, has rapidly spread worldwide, causing a global pandemic. In addition to respiratory symptoms, the virus can also affect the gastrointestinal system. GI symptoms such as anorexia, abdominal pain, nausea, vomiting, and diarrhea have been reported. The virus can potentially be transmitted through the fecal-oral route, and viral RNA has been detected in blood samples of infected patients, indicating hematologic dissemination.
Article
Virology
Mallory T. Barbier, Luis Del Valle
Summary: This study reports a case of an AIDS-related multifocal primary CNS lymphoma in which JCPyV genomic sequences and T-Antigen expression were detected, but active replication of JCPyV was ruled out. Sequencing revealed the presence of Mad-4 strain of JCPyV in tumor cells. Furthermore, expression of viral proteins from Epstein-Barr virus was also detected, suggesting a potential collaboration between these two viruses in the malignant transformation process of B-lymphocytes.
Article
Oncology
Michele Vigolo, Charlotte Urech, Sebastien Lamy, Giulia Monticone, Jovanny Zabaleta, Fokhrul Hossain, Dorota Wyczechowska, Luis Del Valle, Ruth M. O'Regan, Lucio Miele, Rajwinder Lehal, Samarpan Majumder
Summary: Notch signaling is involved in treatment resistance and cancer stem cell maintenance in breast cancer. CB-103 is a novel pan-Notch inhibitor with improved safety and efficacy compared to first-generation inhibitors. The study demonstrates that CB-103 in combination with fulvestrant or paclitaxel exhibits promising therapeutic potential in endocrine-resistant and triple negative breast cancers.
Meeting Abstract
Oncology
Fokhrul Hossain, Denise Danos, Jovanny Zabaleta, Jiande Wu, Mary Anne Lynch, Luis Del Valle, Xiao-Cheng Wu, Augusto Ochoa, Chindo Hicks, Lucio Miele