Editorial Material
Oncology
Cedric Rossi, Rene-Olivier Casasnovas
Summary: Novel targeted approaches have significantly improved the prognosis of patients with relapsed/refractory Hodgkin lymphoma, especially with the use of inhibitors like Nivolumab and pembrolizumab.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Oncology
Yuxuan Che, Xiaolei Ding, Liye Xu, Jian Zhao, Xian Zhang, Na Li, Xiuhua Sun
Summary: Hodgkin's lymphoma (HL) is a unique B-cell lymphoproliferative malignancy, characterized by a sparse population of Hodgkin and Reed-Sternberg cells and dysfunctional immune cells. Although systemic chemotherapy has improved the prognosis of most patients, some still have poor response or relapse. Novel strategies, including targeted therapies, immunotherapy, and cell therapy, have emerged with the increased understanding of HL biology and microenvironment. This review summarizes the progress in developing novel therapies for HL and discusses future research directions.
INTERNATIONAL JOURNAL OF ONCOLOGY
(2023)
Review
Oncology
Heather A. Lillemoe, Roberto N. Miranda, Loretta J. Nastoupil, Mark W. Clemens, Kelly K. Hunt
Summary: Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare lymphoma that arises in response to textured-surface breast implants. It typically presents as swelling around the implant after breast reconstruction or cosmetic augmentation, but can also manifest as invasive masses or enlarged lymph nodes. There is currently limited surgical guidance for patients with more aggressive BIA-ALCL presentations.
ANNALS OF SURGICAL ONCOLOGY
(2022)
Editorial Material
Hematology
Peter W. M. Johnson
Summary: The study shows that treating relapsed or refractory HL with PD-1 antibody nivolumab has a high response rate, making it an attractive option for second-line therapy.
Review
Immunology
Jennifer E. Agrusa, Emily R. Egress, Eric J. Lowe
Summary: ALCL is the most common mature T-cell non-Hodgkin lymphoma in children/adolescents, and improved therapies are needed. Brentuximab vedotin, an anti-CD30 antibody-drug conjugate, has shown safety and efficacy in clinical trials for ALCL in both pediatric and adult populations. Future studies should investigate combination therapies with brentuximab vedotin and other targeted agents.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Rosalaura V. Villarreal-Gonzalez, Sandra N. Gonzalez-Diaz, Wendy J. Santos-Fernandez, Perla R. Colunga-Pedraza, Ana Laura Varela-Constantino, David Gomez-Almaguer
Summary: Brentuximab vedotin (BV) is a monoclonal antibody used for the treatment of CD30+ lymphomas and classical Hodgkin lymphoma (HL). This article presents three cases of refractory HL patients who experienced anaphylaxis to BV administration and discusses a desensitization protocol used for their treatment. The results suggest that desensitization may be a viable strategy for patients with relapsed or refractory HL.
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
(2022)
Article
Oncology
Ying Li, Ligang Liu, Hao Sun, Nan Li, Shuang Huang, Alexander Olinger, Xiaolin Xu, Xiaoling Wang, Yanlong Duan
Summary: This article reports the treatment experience of a pediatric Hodgkin's lymphoma patient with TTN gene mutation and heart failure. The combination of Brentuximab Vedotin (BV) and chemotherapy achieved good efficacy and tolerability in this patient without the use of anthracycline anticancer drugs.
FRONTIERS IN ONCOLOGY
(2022)
Article
Medicine, General & Internal
Stephen M. Ansell, John Radford, Joseph M. Connors, Monika Dlugosz-Danecka, Won-Seog Kim, Andrea Gallamini, Radhakrishnan Ramchandren, Jonathan W. Friedberg, Ranjana Advani, Martin Hutchings, Andrew M. Evens, Piotr Smolewski, Kerry J. Savage, Nancy L. Bartlett, Hyeon-Seok Eom, Jeremy S. Abramson, Cassie Dong, Frank Campana, Keenan Fenton, Markus Puhlmann, David J. Straus
Summary: The study found that using A+AVD for the treatment of stage III or IV Hodgkin's lymphoma provides a survival advantage over ABVD.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Review
Oncology
Walter Hanel, Alex F. Herrera, Narendranath Epperla
Summary: The treatment landscape of classical Hodgkin lymphoma has significantly changed in the past 20 years, with improvements in patient management and increased complexity in treatment approaches. By incorporating new drugs and adjusting treatment sequences, long-term remission can be achieved, and treatment advancements are expected to continue with ongoing clinical trials.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Review
Oncology
Radhika Takiar, Yasmin Karimi
Summary: This article reviews salvage therapy options for relapsed/refractory classical Hodgkin's lymphoma and discusses the use of novel agents in treatment, providing a proposed algorithm for determining the appropriate treatment approach for this patient population.
Review
Surgery
Hani Naga, Joseph A. Mellia, Marten N. Basta, Martin P. Morris, Adrienne N. Christopher, Frank M. Campbell, Katie Sommers, Howard Levinson, Jonas A. Nelson, John P. Fischer
Summary: This study assessed current treatment strategies for breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). The results showed that current guidelines focus on the treatment of local disease and reduce nonsurgical interventions. Patients with advanced BIA-ALCL have higher rates of recurrence and mortality.
PLASTIC AND RECONSTRUCTIVE SURGERY
(2022)
Article
Oncology
Xudong Zhang, Honghan Qiao, Xiaofei Chai, Xue Gao, Rongjun Ma, Yufu Li, Zunmin Zhu, Mingzhi Zhang
Summary: This study retrospectively investigated the real-world application of BV in lymphoma patients in different hospitals in Henan province, China. The results showed that BV had remarkable therapeutic effectiveness and moderate toxicity in Chinese lymphoma patients.
Review
Hematology
Maliha Khan, Fredrick Hagemeister, Michael Wang, Sairah Ahmed
Summary: This article discusses the classification of Hodgkin lymphoma, the biology of classical Hodgkin lymphoma (cHL), and the available treatment options for relapsed cHL. Brentuximab vedotin and immune checkpoint inhibitors have shown efficacy in the treatment of cHL, and chimeric antigen receptor T-cell therapy is being explored as a potential treatment option.
Article
Oncology
Rosalaura V. Villarreal-Gonzalez, Sandra N. Gonzalez-Diaz, Cindy E. de Lira-Quezada, David Gomez-Almaguer, Andres Gomez-De Leon, Natalhie Acuna-Ortega
Summary: This case report describes a 23-year-old female patient with severe anaphylaxis reaction to brentuximab vedotin, which was successfully controlled with desensitization treatment. Rapid drug desensitization may be a favorable option for patients experiencing severe hypersensitivity reactions.
JOURNAL OF ONCOLOGY PHARMACY PRACTICE
(2021)
Article
Oncology
Davide Massano, Elisa Carraro, Lara Mussolin, Salvatore Buffardi, Veronica Barat, Daniele Zama, Paola Muggeo, Francesca Vendemini, Antonella Sau, Maria Luisa Moleti, Federico Verzegnassi, Salvatore D'Amico, Tommaso Casini, Alberto Garaventa, Elisabetta Schiavello, Monica Cellini, Luciana Vinti, Piero Farruggia, Katia Perruccio, Simone Cesaro, Raffaela De Santis, Maddalena Marinoni, Irene D'Alba, Rosa Maria Mura, Roberta Burnelli, Maurizio Mascarin, Marta Pillon
Summary: This study evaluated the safety and efficacy of Brentuximab vedotin (BV) in pediatric patients with refractory/relapsed Hodgkin's lymphoma (HL) aged less than 18 years. The results showed that BV, either as monotherapy or in combination with other therapies, was a safe and effective drug, able to induce complete remission with a high response rate and favorable progression-free survival and overall survival.
PEDIATRIC BLOOD & CANCER
(2022)
Article
Psychiatry
Ruin Moaddel, Panos Zanos, Cristan A. Farmer, Bashkim Kadriu, Patrick J. Morris, Jacqueline Lovett, Elia E. Acevedo-Diaz, Grace W. Cavanaugh, Peixiong Yuan, Mani Yavi, Craig J. Thomas, Lawrence T. Park, Luigi Ferrucci, Todd D. Gould, Carlos A. Zarate
Summary: Subanesthetic-dose ketamine has rapid and sustained antidepressant effects, and its metabolite (2 R,6 R)-HNK also exhibits similar effects. Metabolomic analysis reveals the involvement of inflammatory pathways in the effects of ketamine and (2 R,6 R)-HNK, with potential differences between mice and humans.
TRANSLATIONAL PSYCHIATRY
(2022)
Article
Oncology
Roma Pahwa, Janhavi Dubhashi, Anand Singh, Parthav Jailwala, Alexei Lobanov, Craig J. Thomas, Michele Ceribelli, Kelli Wilson, Christopher J. Ricketts, Cathy D. Vocke, Catherine Wells, Donald P. Bottaro, W. Marston Linehan, Len Neckers, Ramaprasad Srinivasan
Summary: The HSP90 inhibitor SNX2112 has shown significant anti-tumor activity against advanced papillary renal cell carcinoma (PRCC) by inhibiting MET and downstream mediators, as well as a unique set of genes associated with the G2M cell cycle. The study also suggests that overexpression of these genes may indicate a poor prognosis in PRCC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Dan He, Huijin Feng, Belen Sundberg, Jiaxing Yang, Justin Powers, Alec H. Christian, John E. Wilkinson, Cian Monnin, Daina Avizonis, Craig J. Thomas, Richard A. Friedman, Michael D. Kluger, Michael A. Hollingsworth, Paul M. Grandgenett, Kelsey A. Klute, F. Dean Toste, Christopher J. Chang, Iok In Christine Chio
Summary: Loss of MSRA, a suppressor of PDA metastasis, leads to the oxidation of methionine residue M239 in PKM2, promoting migration and metastasis of tumor cells.
Article
Hematology
Joshua Bennett, Chiharu Ishikawa, Puneet Agarwal, Jennifer Yeung, Avery Sampson, Emma Uible, Eric Vick, Lyndsey C. Bolanos, Kathleen Hueneman, Mark Wunderlich, Amal Kolt, Kwangmin Choi, Andrew Volk, Kenneth D. Greis, Jan Rosenbaum, Scott B. Hoyt, Craig J. Thomas, Daniel T. Starczynowski
Summary: This study reveals the functional compensation and complementation of IRAK1 in leukemic cells upon inhibition of IRAK4. Cotargeting IRAK1 and IRAK4 is necessary to suppress leukemic stem/progenitor cell function and induce differentiation. IRAK1 and IRAK4 maintain the undifferentiated state of MDS/AML LSPCs through noncanonical MyD88-independent pathways.
Article
Oncology
Tyler J. Peat, Snehal M. Gaikwad, Wendy Dubois, Nana Gyabaah-Kessie, Shuling Zhang, Sayeh Gorjifard, Zaw Phyo, Megan Andres, Keith Hughitt, R. Mark Simpson, Margaret A. Miller, Andrew T. Girvin, Andrew Taylor, Daniel Williams, Nelson D'Antonio, Yong Zhang, Adhithi Rajagopalan, Evan Flietner, Kelli Wilson, Xiaohu Zhang, Paul Shinn, Carleen Klumpp-Thomas, Crystal McKnight, Zina Itkin, Lu Chen, Dickran Kazandijian, Jing Zhang, Aleksandra M. Michalowski, John K. Simmons, Jonathan Keats, Craig J. Thomas, Beverly A. Mock
Summary: Drug resistance and disease progression are common in MM patients. A study identified 43 potentially synergistic combinations through drug screening and in silico analysis. These combinations effectively reduce MYC expression and enhance p16 activity, leading to improved viability and prolonged survival in MM models.
Article
Oncology
William C. Reinhold, Kelli Wilson, Fathi Elloumi, Katie R. Bradwell, Michele Ceribelli, Sudhir Varma, Yanghsin Wang, Damien Duveau, Nikhil Menon, Jane Trepel, Xiaohu Zhang, Carleen Klumpp-Thomas, Samuel Micheal, Paul Shinn, Augustin Luna, Craig Thomas, Yves Pommier
Summary: Significant progress has been made in precision medicine for cancer treatment, but there are still unanswered questions that need to be addressed. CellMinerCDB: NCATS is a web application that provides activity information for various drugs and compounds, including nononcology drugs and unique compounds. It integrates multiple forms of data and offers analysis tools for exploring drug response in cancer cell lines.
Article
Chemistry, Multidisciplinary
Brice Martin, Tyler Garman, Madeline Laramee, Amy Wang, Xiaohu Zhang, Erin Beck, Kelli Wilson, Carleen Klumpp-Thomas, Crystal McKnight, Xin Xu, Natalie Hagen, David Holland, Nadia Dahmane, Craig J. Thomas, Mark Souweidane
Summary: In this study, a high-throughput screen was conducted on a human patient-derived CPC cell line, identifying 427 potential targets and providing new strategies for CPC treatment. Two combination therapies (topotecan/elimusertib and melphalan/elimusertib) were validated in vitro and in vivo, leading to increased survival in a CPC genetic mouse model. This study identifies multiple promising combinatorial therapeutics for CPC and highlights the potential of intra-arterial delivery in CPC treatment.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Oncology
Martin Lang, Laura S. Schmidt, Kelli M. Wilson, Christopher J. Ricketts, Carole Sourbier, Cathy D. Vocke, Darmood Wei, Daniel R. Crooks, Youfeng Yang, Benjamin K. Gibbs, Xiaohu Zhang, Carleen Klumpp-Thomas, Lu Chen, Rajarshi Guha, Marc Ferrer, Crystal McKnight, Zina Itkin, Darawalee Wangsa, Danny Wangsa, Amy James, Simone Difilippantonio, Baktir Karim, Francisco Moris, Thomas Ried, Maria J. Merino, Ramaprasad Srinivasan, Craig J. Thomas, W. Marston Linehan
Summary: The study identified several potential therapeutic agents for treating advanced MiT-RCC, including PI3K/mTOR inhibitor NVP-BGT226, transcription inhibitor Mithramycin A, and GPNMB-targeted antibody-drug conjugate CDX-011. Preclinical studies demonstrated the efficacy of these agents in vitro and in vivo, providing potential treatment options for patients with MiT-driven RCC.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Oncology
Junko Murai, Michele Ceribelli, Haiqing Fu, Christophe E. Redon, Ukhyun Jo, Yasuhisa Murai, Mirit I. Aladjem, Craig J. Thomas, Yves Pommier
Summary: Schlafen 11 (SLFN11) is a predictive biomarker and molecular sensor for a wide range of clinical drugs. A high-throughput screen was conducted to identify drugs that target SLFN11, and it was found that the neddylation inhibitor pevonedistat and the DNA polymerase a inhibitor AHPN/CD437 induced SLFN11 chromatin recruitment. Pevonedistat recruited SLFN11 at late time points (24 hours), and SLFN11-deficient cells showed increased unscheduled re-replication after 24 hours. However, SLFN11-proficient cells blocked this re-replication. The study suggests that SLFN11 could serve as a predictive biomarker for pevonedistat in clinical trials.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Oncology
Sebastian Scheich, Jiji Chen, Jiamin Liu, Frank Schnutgen, Julius C. Enssle, Michele Ceribelli, Craig J. Thomas, Jaewoo Choi, Vivian Morris, Tony Hsiao, Hang Nguyen, Boya Wang, Arnold Bolomsky, James D. Phelan, Sean Corcoran, Henning Urlaub, Ryan M. Young, Bjorn Haupl, George W. Wright, Da Wei Huang, Yanlong Ji, Xin Yu, Weihong Xu, Yandan Yang, Hong Zhao, Jagan Muppidi, Kuan-Ting Pan, Thomas Oellerich, Louis M. Staudt
Summary: Diffuse large B-cell lymphoma (DLBCL) can be categorized into two subtypes: activated B-cell (ABC) and germinal center B cell-like (GCB). The study found that self-antigen engagement of B-cell receptors (BCR) in ABC tumors triggers clustering, activating chronic active signaling and NF-KB and PI3 kinase. Genome-wide CRISPR-Cas9 screens were used to identify regulators of IRF4, a direct transcriptional target of NF-KB and an indicator of proximal BCR signaling in ABC DLBCL. Inactivation of N-linked protein glycosylation by the OST-B complex reduced IRF4 expression and targeting OST-B inhibition killed models of ABC and GCB DLBCL, suggesting the potential for selective OST-B inhibitors in treating these aggressive cancers.
Article
Biochemistry & Molecular Biology
David B. Morse, Aleksandra M. Michalowski, Michele Ceribelli, Joachim De Jonghe, Maria Vias, Deanna Riley, Theresa Davies-Hill, Ty Voss, Stefania Pittaluga, Christoph Muus, Jiamin Liu, Samantha Boyle, David A. Weitz, James D. Brenton, Jason D. Buenrostro, Tuomas P. J. Knowles, Craig J. Thomas
Summary: Single-cell RNA sequencing (scRNA-seq) is used to describe cell states, but the spatial arrangement of these states in tissues is challenging. Segmentation by exogenous perfusion (SEEP) is a method that links surface proximity and environment accessibility to transcriptional identity within 3D disease models. Using SEEP, analysis of ovarian cancer models reveals the relationship between cell state and position, and shows how microenvironments influence individual cell identities.
Article
Biochemical Research Methods
Emma J. Chory, Meng Wang, Michele Ceribelli, Aleksandra M. Michalowska, Stefan Golas, Erin Beck, Carleen Klumpp-Thomas, Lu Chen, Crystal McKnight, Zina Itkin, Kelli M. Wilson, David Holland, Sanjay Divakaran, James Bradner, Javed Khan, Berkley E. Gryder, Craig J. Thomas, Benjamin Z. Stanton
Summary: We conducted a comprehensive study on drug synergy in acute myeloid leukemia (AML), using a panel of cell lines representing different subtypes. Our study provides a valuable resource for the community, offering many unexpected synergistic drug combinations and open source code for automation and analysis. We identified drug synergies that affect the chromatin state, particularly in relation to the modification of histone H3 lysine-27. Additionally, we developed an open source high throughput methodology that allows multidimensional drug screening with widely accessible equipment.
Article
Medicine, Research & Experimental
Anju Kumari, Lisa Gesumaria, Yan-Jin Liu, V. Keith Hughitt, Xiaohu Zhang, Michele Ceribelli, Kelli M. Wilson, Carleen Klumpp-Thomas, Lu Chen, Crystal McKnight, Zina Itkin, Craig J. Thomas, Beverly A. Mock, David S. Schrump, Haobin Chen
Summary: Small cell lung cancer (SCLC) is a difficult-to-treat malignancy and current treatment options are limited. This study identified that mTOR inhibitors (mTORis) show the highest synergy with BET inhibitors (BETis) in SCLC, enhancing their antitumor activities both in vitro and in vivo. Mechanistically, BETis induce apoptosis in SCLC by activating the intrinsic apoptotic pathway, but also upregulate RSK3 to promote survival. However, mTORis block this survival signaling and augment the apoptosis induced by BET inhibition. Combination therapy of mTORis and BETis has potential for further evaluation in SCLC patients.
Article
Multidisciplinary Sciences
Nishanth Ulhas Nair, Patricia Greninger, Xiaohu Zhang, Adam A. Friedman, Arnaud Amzallag, Eliane Cortez, Avinash Das Sahu, Joo Sang Lee, Anahita Dastur, Regina K. Egan, Ellen Murchie, Michele Ceribelli, Giovanna S. Crowther, Erin Beck, Joseph McClanaghan, Carleen Klump-Thomas, Jessica L. Boisvert, Leah J. Damon, Kelli M. Wilson, Jeffrey Ho, Angela Tam, Crystal McKnight, Sam Michael, Zina Itkin, Mathew J. Garnett, Jeffrey A. Engelman, Daniel A. Haber, Craig J. Thomas, Eytan Ruppin, Cyril H. Benes
Summary: Combination of anti-cancer drugs is commonly used to overcome limited efficacy of single agents. Designing and testing combinations are challenging due to the heterogeneity of tumor response. Co-targeting functionally proximal genes may result in higher efficacy, offering a strategy for more efficient combinations.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Jerry T. Wu, Adam Cheuk, Kristine Isanogle, Christina Robinson, Xiaohu Zhang, Michele Ceribelli, Erin Beck, Paul Shinn, Carleen Klumpp-Thomas, Kelli M. Wilson, Crystal Mcknight, Zina Itkin, Hiroshi Sotome, Hiroshi Hirai, Elizabeth Calleja, Volker Wacheck, Brad Gouker, Cody J. Peer, Natalia Corvalan, David Milewski, Yong Y. Kim, William D. Figg, Elijah F. Edmondson, Craig J. Thomas, Simone Difilippantonio, Jun S. Wei, Javed Khan
Summary: Rhabdomyosarcoma (RMS) is a common pediatric soft tissue sarcoma. Futibatinib, an irreversible pan-FGFR inhibitor, shows efficacy in inhibiting the growth of RMS cell lines in vitro by targeting FGFR4. However, limited efficacy is observed in animal models, suggesting the need for alternative treatment strategies.