Oncotarget

A new research paper was published in Oncotarget's Volume 14 on February 11, 2023, entitled, “Oncogenic driver FGFR3-TACC3 requires five coiled-coil heptads for activation and disulfide bond formation for stability.”

FGFR3-TACC3 represents an oncogenic fusion protein frequently identified in glioblastoma, lung cancer, bladder cancer, oral cancer, head and neck squamous cell carcinoma, gallbladder cancer, and cervical cancer. Various exon breakpoints of FGFR3-TACC3 have been identified in cancers. In this recent study, researchers Clark G. Wang, Malalage N. Peiris, April N. Meyer, Katelyn N. Nelson, and Daniel J. Donoghue from University of California San Diego analyzed these FGFR3-TACC3 exon breakpoints to determine the minimum contribution of TACC3 for activation of the FGFR3-TACC3 fusion protein.

“In this work, we characterize the signaling, transforming abilities, and post-translational modifications of FGFR3-TACC3 fusion proteins arising from different exonic breakpoints to determine the requirements for dimerization and constitutive activation of the fusion protein.”

While TACC3 exons 11 and 12 are dispensable for activity, the researchers’ results show that FGFR3-TACC3 requires exons 13-16 for biological activity. A detailed analysis of exon 13, which consists of 8 heptads forming a coiled coil, further defined the minimal region for biological activity as consisting of 5 heptads from exon 13, in addition to exons 14-16.

These conclusions were supported by transformation assays of biological activity, examination of MAPK pathway activation, analysis of disulfide-bonded FGFR3-TACC3, and by examination of the Endoglycosidase H-resistant portion of FGFR3-TACC3. These results demonstrate that clinically identified FGFR3-TACC3 fusion proteins differ in their biological activity, depending upon the specific breakpoint. This study further suggests the TACC3 dimerization domain of FGFR3-TACC3 as a novel target in treating FGFR translocation driven cancers.

“Taken together, these results provide a better understanding of the mechanism for activation of FGFR3-TACC3 and narrow the scope of targeting TACC3 to create effective dimerization disruption-based therapies for treating patients with FGFR3-TACC3 driven tumors.”

DOI: https://doi.org/10.18632/oncotarget.28359

Correspondence to: Daniel J. Donoghue - [email protected]

Keywords: oncogenic fusion protein, chromosomal translocation, glioblastoma, FGFR3-TACC3, coiled-coil

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Crossref is a non-profit organization that logs and updates citations for scientific publications. Each month, Crossref identifies a list of the most popular Oncotarget papers based on the number of times a DOI is successfully resolved. Below are Crossref’s Top 10 Oncotarget DOIs in 2022.

10: Cell fusion as a link between the SARS-CoV-2 spike protein, COVID-19 complications, and vaccine side effects

DOI: https://doi.org/10.18632/oncotarget.28088

Author: Yuri Lazebnik

9: A Jurkat 76 based triple parameter reporter system to evaluate TCR functions and adoptive T cell strategies

DOI: https://doi.org/10.18632/oncotarget.24807

Authors: Sandra Rosskopf, Judith Leitner, Wolfgang Paster, Laura T. Morton, Renate S. Hagedoorn, Peter Steinberger, and Mirjam H.M. Heemskerk

8: IL-37 suppresses hepatocellular carcinoma growth by converting pSmad3 signaling from JNK/pSmad3L/c-Myc oncogenic signaling to pSmad3C/P21 tumor-suppressive signaling

DOI: https://doi.org/10.18632/oncotarget.13196

Authors: Rui Liu, Chengyong Tang, Ai Shen, Huating Luo, Xufu Wei, Daofeng Zheng, Chao Sun, Zhongtang Li, Di Zhu, Tingting Li, and Zhongjun Wu

7: Apatinib-based targeted therapy against pulmonary sarcomatoid carcinoma: a case report and literature review

DOI: https://doi.org/10.18632/oncotarget.25989

Authors: Xiaofeng Li, Yueming He, Jinfeng Zhu, Hongxia Pang, Yongwei Lin, and Jinyang Zheng

6: Treasures from trash in cancer research

DOI: https://doi.org/10.18632/oncotarget.28308

Authors: Fabiano Cordeiro Moreira, Dionison Pereira Sarquis, Jorge Estefano Santana de Souza, Daniel de Souza Avelar, Taíssa Maria Thomaz Araújo, André Salim Khayat, Sidney Emanuel Batista dos Santos, and Paulo Pimentel de Assumpção

5: Real-world survival analysis by tumor mutational burden in non-small cell lung cancer: a multisite U.S. study

DOI: https://doi.org/10.18632/oncotarget.28178

Authors: Connor Willis, Hillevi Bauer, Trang H. Au, Jyothi Menon, Sudhir Unni, Dao Tran, Zachary Rivers, Wallace Akerley, Matthew B. Schabath, Firas Badin, Ashley Sekhon, Malini Patel, Bing Xia, Beth Gustafson, John L. Villano, John-Michael Thomas, Solomon J. Lubinga, Michael A. Cantrell, Diana Brixner, and David Stenehjem

4: Continuous treatment with abemaciclib leads to sustained and efficient inhibition of breast cancer cell proliferation

DOI: https://doi.org/10.18632/oncotarget.28249

Authors: Raquel Torres-Guzmán, Maria Patricia Ganado, Cecilia Mur, Carlos Marugan, Carmen Baquero, Yanzhu Yang, Yi Zeng, Huimin Bian, Jian Du, Alfonso de Dios, Oscar Puig, and María José Lallena

3: Increased gut permeability in cancer cachexia: mechanisms and clinical relevance

DOI: https://doi.org/10.18632/oncotarget.24804

Authors: Laure B. Bindels, Audrey M. Neyrinck, Audrey Loumaye, Emilie Catry, Hannah Walgrave, Claire Cherbuy, Sophie Leclercq, Matthias Van Hul, Hubert Plovier, Barbara Pachikian, Luis G. Bermúdez-Humarán, Philippe Langella, Patrice D. Cani, Jean-Paul Thissen, and Nathalie M. Delzenne

2: Inflammatory responses and inflammation-associated diseases in organs

DOI: https://doi.org/10.18632/oncotarget.23208

Authors: Linlin Chen, Huidan Deng, Hengmin Cui, Jing Fang, Zhicai Zuo, Junliang Deng, Yinglun Li, Xun Wang, and Ling Zhao

1: Proteomic profiling of skeletal and cardiac muscle in cancer cachexia: alterations in sarcomeric and mitochondrial protein expression

DOI: https://doi.org/10.18632/oncotarget.25146

Authors: Angie M. Y. Shum, Anne Poljak, Nicholas L. Bentley, Nigel Turner, Timothy C. Tan, and Patsie Polly

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About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

To learn more about Oncotarget, please visit https://www.oncotarget.com

PRESS RELEASE - A new research paper was published in Oncotarget's Volume 14 on February 7, 2023, entitled, “The ‘extreme phenotype approach’ applied to male breast cancer allows the identification of rare variants of ATR as potential breast cancer susceptibility alleles.”

In oncogenetics, some patients could be considered as “extreme phenotypes”, such as those with very early onset presentation or multiple primary malignancies, unusually high numbers of cancers of the same spectrum or rare cancer types in the same parental branch. For these cases, a genetic predisposition is very likely, but classical candidate gene panel analyses often, and frustratingly, remains negative.

In this new study, researchers Martin Chevarin, Diana Alcantara, Juliette Albuisson, Marie-Agnès Collonge-Rame, Céline Populaire, Zohair Selmani, Amandine Baurand, Caroline Sawka, Geoffrey Bertolone, Patrick Callier, Yannis Duffourd, Philippe Jonveaux, Yves-Jean Bignon, Isabelle Coupier, François Cornelis, Christophe Cordier, Monique Mozelle-Nivoix, Jean-Baptiste Rivière, Paul Kuentz, Christel Thauvin, Romain Boidot, François Ghiringhelli, Marc O'Driscoll, Laurence Faivre, and Sophie Nambot from Université de Bourgogne, CHU Dijon Bourgogne, CHU Besançon, University of Sussex, Centre Georges François Leclerc, Université de Bourgogne-Franche Comté, Hôpitaux de Brabois, Centre Jean Perrin, ICM Val d’Aurel, Université Bordeaux, CHU de Bordeaux, CHRU de Strasbourg, and CHU-Reims used a combination of exome sequencing (ES), direct sequencing of Ataxia Telangiectasia and RAD3-related (ATR) in a replication cohort and prospective screening, followed by functional investigations, to report the identification of new candidate variants of ATR as predisposing to breast cancer (BC), including male breast cancer (MBC).

“In the framework of the EX2TRICAN project, exploring unresolved extreme cancer phenotypes, we applied exome sequencing on rare familial cases with male breast cancer, identifying a novel pathogenic variant of ATR (p.Leu1808*).”

ATR has already been suspected as being a predisposing gene to breast cancer in women. The researchers next identified 3 additional ATR variants in a cohort of both male and female with early onset and familial breast cancers (c.7762-2A>C; c.2078+1G>A; c.1A>G). Further molecular and cellular investigations showed impacts on transcripts for variants affecting splicing sites and reduction of ATR expression and phosphorylation of the ATR substrate CHEK1. This work further demonstrates the interest of an extended genetic analysis such as exome sequencing to identify very rare variants that can play a role in cancer predisposition in extreme phenotype cancer cases unexplained by classical cancer gene panels testing.

“In conclusion, this work highlights the possible implication of ATR variants in male and female BC predisposition and shows the importance of extended genetic analysis in unsolved extreme phenotype cancer cases to identify rare alleles of biologically relevant candidate genes of cancer predisposition.”

DOI: https://doi.org/10.18632/oncotarget.28358

Correspondence to: Sophie Nambot - [email protected]

Keywords: male breast cancer, genetic predisposition to cancer, exome sequencing, ATR, extreme phenotype

Blog summary of an Editorial was published in Oncotarget, entitled, “Permeability and driving force: why is it difficult to control glycolytic flux by blocking lactate transporters?“

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The process of glycolysis, or the conversion of glucose to energy in cells, is a critical component of many biological processes. This process is highly regulated, and glycolytic flux has been implicated in a variety of disease states, including cancer and diabetes. Despite significant advances in our understanding of glycolysis, researchers continue to find it difficult to control glycolytic flux.

“Overall, glycolysis facilitates tumour proliferation and survival, and has become a hotly-pursued target for therapeutic inhibition.”

In a new editorial paper, researchers Wiktoria Blaszczak and Pawel Swietach from the University of Oxford explored the challenges of this issue and potential solutions. On January 26, 2023, their editorial was published in Oncotarget and entitled, “Permeability and driving force: why is it difficult to control glycolytic flux by blocking lactate transporters?“

“In our recent study (Blaszczak et al. (2022)), using a panel of pancreatic ductal adenocarcinoma cell lines, we characterised how extracellular acidity feeds back to inhibit further glycolytic acid production [6].”

Full blog - https://www.oncotarget.org/2023/02/16/controlling-glycolytic-flux-therapy-challenges-and-solutions/

DOI - https://doi.org/10.18632/oncotarget.28351 (PDF Download)

Correspondence to - Wiktoria Blaszczak - [email protected]

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Keywords - MCT inhibitors, fermentative metabolism, lactate, PDAC, SLC16A1

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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A new research paper was published in Oncotarget's Volume 14 on January 31, 2023, entitled, “Novel inflammation-combined prognostic index to predict survival outcomes in patients with gastric cancer.”

In vivo inflammatory responses are involved in cancer growth, invasion and metastasis, and the involvement of systemic inflammatory responses and the surrounding microenvironment is intricately intertwined. In this recent study, researchers Noriyuki Hirahara, Takeshi Matsubara, Shunsuke Kaji, Hikota Hayashi, Yohei Sasaki, Koki Kawakami, Ryoji Hyakudomi, Tetsu Yamamoto, and Yoshitsugu Tajima from Shimane University Faculty of Medicine and Matsue Red Cross Hospital in Japan focused on the lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and devised an inflammation-combined prognostic index (ICPI) as a prognostic marker of cancer-specific survival (CSS).

“We reviewed the clinicopathological data of 480 patients with gastric cancer undergoing curative laparoscopic gastrectomy between 2009 and 2019. This study examined the significance of LMR, NLR, PLR, and ICPI as cancer-specific prognostic markers.”

In univariate analysis, tumor diameter, histological differentiation, pathological tumor-node-metastasis (pTNM) stage, LMR, NLR, PLR, C-reactive protein (CRP) level, carcinoembryonic antigen (CEA), and postoperative chemotherapy were significantly associated with CSS. In multivariate analysis, pTNM stage and CEA were the independent risk factors for CSS, although LMR, NLR, and PLR were not the independent risk factors for CSS.

The ICPI formula was constructed using hazard ratios for three inflammation-based biomarkers with worse prognosis identified in the univariate analysis: LMR <4.315, NLR ≥2.344, and PLR ≥212.01, which were each scored as 1, with all remaining values pointed at 0. ICPI was calculated as follows: ICPI = 2.9 × LMR + 2.8 × NLR + 2.8 × PLR. The optimal cutoff value of ICPII was 2.9. On multivariate analysis, pTNM stage, CEA, and ICPI were independent prognostic factors for CSS. In the Kaplan–Meier survival analysis, CSS in the high ICPI group was significantly worse than that in the low ICPI group. ICPI was devised as a novel predictive index for prognosis, and its usefulness was clarified.

“In this study, the ICPI was devised as a novel predictive index of prognosis, and its usefulness was clarified. However, it is still unclear how active preoperative intervention using the ICPI as an indicator will contribute to improved oncological prognosis. In the future, it will be necessary to conduct a multicenter prospective study to examine the prognostic effect of preoperative interventions, including nutrition.”

DOI: https://doi.org/10.18632/oncotarget.28353

Correspondence to: Noriyuki Hirahara - [email protected]

Keywords: gastric cancer, laparoscopic gastrectomy, novel predictive index, inflammation-combined prognostic index, cancer-specific survival

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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A new research paper was published in Oncotarget's Volume 14 on February 2, 2023, entitled, “Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC).”

TP53 mutant head and neck squamous cell carcinoma (HNSCC) patients exhibit poor clinical outcomes with 50–60% recurrence rates in advanced stage patients. In a recent phase II clinical trial, adjuvant therapy with everolimus (mTOR inhibitor) significantly increased 2-year progression-free survival in p53 mutated patients. TP53-driven mTOR activation in solid malignancies causes upregulation of HIF-1α and its target, downstream effector VEGF, by activating STAT3 cell signaling pathway.

In this recent study, researchers Md Maksudul Alam, Janmaris Marin Fermin, Mark Knackstedt, Mackenzie J. Noonan, Taylor Powell, Landon Goodreau, Emily K. Daniel, Xiaohua Rong, Tara Moore-Medlin, Alok R. Khandelwal, and Cherie-Ann O. Nathan from LSU-Health Sciences Center investigated the effects of everolimus on the STAT3/HIF-1α/VEGF pathway in TP53 mutant cell lines and xenograft models.

“The role of mTOR inhibitors (mTORi) as potent growth inhibitory and antiangiogenic/anti-lymphangiogenic agents in HNSCC is well established [18]. Moreover, mTORi significantly suppressed baseline invasiveness of endothelial and HNSCC tumor cells [19]. However, the underlying molecular mechanisms for mutant p53 protein-mediated activation of the mTOR pathway which drive the oncologic processes in HNSCC are yet to be elucidated.”

Treatment with everolimus significantly inhibited cell growth in vitro and effectively reduced the growth of TP53 mutant xenografts in a minimal residual disease (MRD) model in nude mice. Everolimus treatment was associated with significant downregulation of STAT3/HIF-1α/VEGF pathway in both models. Further, treatment with everolimus was associated with attenuation in tumor angiogenesis and lymphangiogenesis as indicated by decreased microvessel density of vascular and lymphatic vessels in HN31 and FaDu xenografts. Everolimus downregulated the STAT3/HIF-1α/VEGF pathway to inhibit growth and in vitro tube formation of HMEC-1 (endothelial) and HMEC-1A (lymphatic endothelial) cell lines.

“Our studies demonstrated that everolimus inhibits the growth of TP53 mutant tumors by inhibiting angiogenesis and lymphangiogenesis through the downregulation of STAT3/HIF-1α/VEGF signaling.”

DOI: https://doi.org/10.18632/oncotarget.28355

Correspondence to: Cherie-Ann O. Nathan - [email protected]

Keywords: TP53 mutant, HNSCC, angiogenesis, everolimus, mTOR

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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A new research perspective was published in Oncotarget's Volume 14 on February 4, 2023, entitled, “The immunoregulatory protein CD200 as a potentially lucrative yet elusive target for cancer therapy.”

CD200 is an immunoregulatory cell surface ligand with proven pro-tumorigenic credentials via its ability to suppress CD200 receptor (CD200R)-expressing anti-tumor immune function. This definitive role for the CD200-CD200R axis in regulating an immunosuppressive tumor microenvironment has garnered increasing interest in CD200 as a candidate target for immune checkpoint inhibition therapy.

However, while the CD200 blocking antibody samalizumab is still in the early stages of clinical testing, alternative mechanisms for the pro-tumorigenic role of CD200 have recently emerged that extend beyond direct suppression of anti-tumor T cell responses and, as such, may not be susceptible to CD200 antibody blockade.

In this new research perspective, researchers Anqi Shao and David M. Owens from Columbia University Irving Medical Center summarized the current understanding of CD200 expression and function in the tumor microenvironment as well as alternative strategies for potential neutralization of multiple CD200 mechanisms in human cancers.

“In the future, unbiased genomic- and proteomic-based approaches may help to clarify these issues by identifying tumor-specific mechanisms of CD200 expression regulation across a variety of human cancers that may be leveraged for broader therapeutic benefit.”

DOI: https://doi.org/10.18632/oncotarget.28354

Correspondence to: David M. Owens - [email protected]

Keywords: CD200 receptor, oncoimmunology, immunotherapy, tumor microenvironment, immune checkpoint inhibition

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Listen to a blog summary on a trending editorial published in Volume 14 of Oncotarget: “To be or not to be: the role of CD56 in multiple myeloma.”

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Multiple myeloma (MM) is a type of blood cancer that affects plasma cells in the bone marrow. These plasma cells, which are responsible for producing antibodies, become abnormal and begin to grow uncontrollably. This results in a buildup of abnormal cells in the bone marrow, leading to decreased production of healthy blood cells, bone damage and a host of other symptoms. MM is incredibly heterogenic, and this variability often leads to unsatisfactory long-term treatment outcomes in many patients with MM. Targets for new treatments and biomarkers of response are needed to improve patient outcomes.

In a new editorial paper published in Oncotarget, researchers Francesca Cottini and Don Benson from The Ohio State University discuss a 2022 research paper they co-authored in which CD56 (or neuronal cell adhesion molecule; NCAM1) was thoroughly described as a biomarker and therapeutic target in multiple myeloma. On January 26, 2023, their editorial about this research paper was published in Oncotarget, entitled, “To be or not to be: the role of CD56 in multiple myeloma.”

“Among others, CD56 is present at variable levels in approximately 70% of patients with multiple myeloma; however, very little is known about CD56 role in multiple myeloma.” (2022 Cottini et al.)

Full blog - https://www.oncotarget.org/2023/02/02/the-importance-of-cd56-in-the-fight-against-multiple-myeloma/

DOI - https://doi.org/10.18632/oncotarget.28350 (PDF Download)

Correspondence to - Francesca Cottini - [email protected]

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Keywords - myeloma, targeted therapies, CD56, signaling

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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A new research paper was published in Oncotarget's Volume 14, entitled, “Spleen tyrosine kinase/FMS-like tyrosine kinase-3 inhibition in relapsed/refractory B-cell lymphoma, including diffuse large B-cell lymphoma: updated data with mivavotinib (TAK-659/CB-659).”

Researchers Leo I. Gordon, Reem Karmali, Jason B. Kaplan, Rakesh Popat, Howard A. Burris III, Silvia Ferrari, Sumit Madan, Manish R. Patel, Giuseppe Gritti, Dima El-Sharkawi, F. Ian Chau, John Radford, Jaime Pérez de Oteyza, Pier Luigi Zinzani, Swaminathan P. Iyer, William Townsend, Harry Miao, Igor Proscurshim, Shining Wang, Shilpi Katyayan, Ying Yuan, Jiaxi Zhu, Kate Stumpo, Yaping Shou, Cecilia Carpio, and Francesc Bosch from Northwestern University Feinberg School of Medicine, Robert H. Lurie Comprehensive Cancer Center, University College London Hospitals, Sarah Cannon Research Institute/Tennessee Oncology, Ospedale Papa Giovanni XXIII, University of Texas Health Science Center, Florida Cancer Specialists/Sarah Cannon Research Institute, Royal Marsden Hospital, The Christie NHS Foundation Trust and University of Manchester, Hospital Universitario HM Sanchinarro, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Università di Bologna, Houston Methodist Cancer Center, Takeda Development Center Americas, Inc. (TDCA), Vall d’Hebron Hospital Universitari, Universitat Autònoma de Barcelona, University of Texas MD Anderson Cancer Center, and Labcorp Drug Development report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib. They present data for the overall cohort of lymphoma patients and the subgroup of patients with diffuse large B-cell lymphoma (DLBCL), including an expanded cohort not included in the initial report.

“Mivavotinib (TAK-659/CB-659) is an investigational, oral, reversible, potent dual inhibitor of spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 (FLT3) [18]. SYK is an essential component of the B-cell receptor signaling pathway; abnormal SYK signaling has been implicated in the pathogenesis of DLBCL and several other B-cell malignancies.”

Patients with relapsed/refractory lymphoma for which no standard treatment was available received mivavotinib 60–120 mg once daily in 28-day cycles until disease progression/unacceptable toxicity. A total of 124 patients with lymphoma, including 89 with DLBCL, were enrolled. Overall response rates (ORR) in response-evaluable patients were 45% (43/95) and 38% (26/69), respectively. Median duration of response was 28.1 months overall and not reached in DLBCL responders.

In subgroups with DLBCL of germinal center B-cell (GCB) and non-GCB origin, ORR was 28% (11/40) and 58% (7/12), respectively. Median progression free survival was 2.0 and 1.6 months in the lymphoma and DLBCL cohorts, respectively. Grade ≥3 treatment-emergent adverse events occurred in 96% of all lymphoma patients, many of which were limited to asymptomatic laboratory abnormalities; the most common were increased amylase (29%), neutropenia (27%), and hypophosphatemia (26%).

“These findings support SYK as a potential therapeutic target for the treatment of patients with B-cell lymphomas, including DLBCL.”

DOI: https://doi.org/10.18632/oncotarget.28352

Correspondence to: Leo I. Gordon - [email protected]

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed.

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A new research perspective was published in Oncotarget's Volume 14 on January 12, 2023, entitled, “Intraventricular immunovirotherapy; a translational step forward.”

In this new perspective, researchers Joshua D. Bernstock, Sarah Blitz, Kyung-Don Kang, and Gregory K. Friedman from Harvard Medical School, Massachusetts Institute of Technology and University of Alabama at Birmingham discuss oncolytic virotherapy with intratumoral engineered type-1 herpes simplex virus (HSV). Intraventricular therapy (IVT) has been proven safe with promising efficacy in recent clinical trials for treatment of both pediatric and adult high-grade glioma.

“Oncolytic herpes simplex virus type-1 (oHSV) has shown promise in clinical trials in both pediatric and adult brain tumors [6–9].”

However, this approach excludes patients with tumors in surgically inaccessible and/or eloquent brain regions. Current delivery methods are also unable to access/treat those patients with metastatic disease in the spinal cord and/or leptomeningeal disease. A recent preclinical study has paved the way for clinical translation of intraventricular administration of oHSV by identifying and mitigating the toxicity associated with this route for therapeutic benefit in murine models of disseminated medulloblastoma. This work may ultimately allow for targeting of intractable disease and provides a feasible option for the repetitive dosing of clinically relevant immunovirotherapy, G207.

“Overall, demonstrating the safety and efficacy of IVT with G207 is a significant step towards expanding the capabilities of oHSV, paving the way for new clinical trials, and increasing the potential of an already promising therapy.”

DOI: https://doi.org/10.18632/oncotarget.28343

Correspondence to: Joshua D. Bernstock - [email protected], Gregory K. Friedman - [email protected]

Keywords: oncolytic virotherapy, herpes simplex virus (HSV), G207, intraventricular therapy, leptomeningeal disease

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