Cancer Research

Oncotarget

Oncotarget published this trending editorial in Volume 14, entitled, “To be or not to be: the role of CD56 in multiple myeloma" by the researchers from the Department of Internal Medicine, Division of Hematology, College of Medicine, The Ohio State University, Columbus, OH.

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

Correspondence to - : Francesca Cottini - Francesca.cottini@osumc.edu 

Paper Intro

Optimal management of Multiple Myeloma (MM), a disorder of clonal malignant plasmacells (PCs), is hampered by the lack of strategies to treat specific subsets of patients. Despite genetic, epigenetic, and mutational heterogeneity, every patient still receives similar regimens without accounting for this variability. This can lead to unsatisfactory or short-lasting responses especially in the relapsed settings or in patients with high-risk chromosomal abnormalities such as t(4;14), 1q21+, or deletion(17p) [1]. MM cells express on their surface a variety of antigens, which help to discern normal reactive PCs from malignant MM cells [2]. These antigens are also targets for monoclonal antibodies, bispecific engagers, or chimeric T/NK cellular therapy [3, 4]. Among them, there is CD56 or NCAM1 (Neuronal Cell adhesion molecule 1), a glycoprotein normally present in neurons, Natural Killer (NK), and T cells, but aberrantly expressed in more than seventy percent of patients with MM [5].

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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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To Be or Not to Be: The Role of CD56 in Multiple Myeloma

Aging (Aging-US)

Aging-US published this trending research perspective in Volume 15, Issue 2, entitled, "Are menopause, aging and prostate cancer diseases?" by Dr. Mikhail V. Blagosklonny from Roswell Park Comprehensive Cancer Center, Buffalo, NY.

DOI - https://doi.org/10.18632/aging.204499

Corresponding author - Mikhail V. Blagosklonny - Blagosklonny@oncotarget.com, Blagosklonny@rapalogs.com 

Abstract

There is no doubt that prostate cancer is a disease. Then, according to hyperfunction theory, menopause is also a disease. Like all age-related diseases, it is a natural process, but is also purely harmful, aimless and unintended by nature. But exactly because these diseases (menopause, prostate enlargement, obesity, atherosclerosis, hypertension, diabetes, presbyopia and thousands of others) are partially quasi-programmed, they can be delayed by slowing aging. Is aging a disease? Aging is a quasi-programmed disease that is partially treatable by rapamycin. On the other hand, aging is an abstraction, a sum of all quasi-programmed diseases and processes. In analogy, the zoo consists of animals and does not exist without animals, but the zoo is not an animal.

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Keywords - aging, geroscience, mTOR, hyperfunction theory of aging, lifespan, healthspan

About Aging-US

Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways.

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Are Menopause, Aging and Prostate Cancer Diseases?

Oncotarget published this research paper in 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)" by the researchers from the Division of Hematology and Oncology, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, IL; Department of Haematology, NIHR/UCLH Clinical Research Facility, University College London Hospitals NHS Foundation Trust, London, UK; Drug Development, Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN; Dipartimento di Oncologia ed Ematologia, Ospedale Papa Giovanni XXIII, Bergamo, Italy; Division of Hematology and Oncology, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio, TX; Drug Development Unit, Florida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL; Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, UK; NIHR Clinical Research Facility, The Christie NHS Foundation Trust and University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; Hematology, Hospital Universitario HM Sanchinarro, Madrid, Spain; IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli”, Bologna, Italy; Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Università di Bologna, Bologna, Italy; Department of Hematology and Oncology, Houston Methodist Cancer Center, Houston, TX; Oncology Clinical Science, Takeda Development Center Americas, Inc. (TDCA), Lexington, MA; Servei d’Hematologia, Vall d’Hebron Hospital Universitari, Experimental Hematology, Vall d’Hebron Institute of Oncology (VHIO), Vall d’Hebron Barcelona Hospital Campus, Barcelona, Spain; Departament de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain; Current affiliation: Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ.

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

Correspondence to - Leo I. Gordon - l-gordon@northwestern.edu 

Abstract

We report an updated analysis from a phase I study of the spleen tyrosine kinase (SYK) and FMS-like tyrosine kinase 3 inhibitor mivavotinib, presenting 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).

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.

Trial registration: ClinicalTrials.gov number: NCT02000934.

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Keywords - Non-Hodgkin’s lymphoma, DLBCL, relapsed/refractory, SYK inhibitor, TAK-659

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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Mivavotinib for Relapsed/Refractory B-cell Lymphoma (Updated)

Technology Networks

In this episode, we will be speaking with *Paul Andrews, Director of Operations at the National Phenotypic Screening Centre, who will be talking to us about drug screening strategies and preclinical drug development. This series is kindly brought to you by CN Bio, click here to find out more: https://bit.ly/2xFrpC1 *(speaker and sponsor are not affiliated)

TSE Explores Drug Discovery - Testing a Drug Compound: Preclinical Screening S05E03

Intraventricular Immunovirotherapy; A Translational Step Forward | Oncotarget
Copy: Oncotarget published this trending research perspective in Volume 14, entitled, “Intraventricular immunovirotherapy; a translational step forward" by the researchers from the Department of Neurosurgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA; David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA; Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Alabama at Birmingham, Birmingham, AL.

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

Correspondence to - Joshua D. Bernstock - jbernstock@bwh.harvard.edu, Gregory K. Friedman - gfriedman@uabmc.edu

Abstract

Oncolytic virotherapy with intratumoral engineered type-1 herpes simplex virus (HSV) has been proven safe with promising efficacy in recent clinical trials for treatment of both pediatric and adult high-grade glioma. 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.

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

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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Intraventricular Immunovirotherapy; A Translational Step Forward

Oncotarget published this research paper in Volume 14, entitled, “The chromatographic constitution of andiroba oil and its healing effects, compared to the LLLT outcomes, in oral mucositis induced in golden Syrian hamsters: a new treatment option" by the researchers from the Department of Dentistry, Federal University of Pará, Guamá, Belém, Pará 66075-970, Brazil; Department of Medicine, University Center of Pará, Souza, Belém, Pará 66613-903, Brazil; Department of Genetics, Laboratory of Human Cytogenetics, Federal University of Pará, Guamá, Belém, Pará 66075-970, Brazil.

DOI - https://doi.org/10.18632/oncotarget.28338

Correspondence to - Diego D.F.A. Alcantara - diegoalcantara@globo.com 

Abstract

The oral mucositis is a mucosal alteration that usually arises from oncological treatments, such as chemotherapy, and it is characterized as an inflammatory process. The aim of this study is to demonstrate the chromatographic constitution of Andiroba oil, comparing and evaluating Andiroba oil and laser scarring efficiency in treatments of oral mucositis in hamsters. These animals were submitted to 5-Fluorouracil. A total of 122 animals were used, randomized and divided into the following groups: (a) positive control; (b) laser associated to andiroba oil; (c) laser; (d) andiroba oil; (e) negative control; (f) cyclophosphamide (genotoxicity control). The induction of oral mucositis occurred by the administration of intraperitoneal Fluorouracila (60 mg/kg) and trauma to the mucosa. The laser protocol was performed once a day and the andiroba oil applied 3 times a day (1,5 ml/day). The mucosae were photographed and removed for clinical and histopathological analysis on day 4, 8, 12 and 15. The analysis was based in OM severity, in specific scoring for the clinical and histopathological aspect. Toxicity was evaluated on day 15 using comet assay and it was performed by variant DNA damage parameters. The data were analysed using analysis of variance (ANOVA) Tukey post-test and Kruskal–Wallis Dunn post-test. The “andiroba oil” and “laser” groups presented better results when compared to the control groups and the treatment associations. The andiroba oil presented the best scarring results, even considering its efficiency proximity to the laser treatment. Andiroba and laser, separately, did not present genotoxicity, however their association evidences damage to DNA.

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Keywords - phytotherapeutic drugs, medical oncology, stomatitis, wound healing, low-level light therapy

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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Healing Effects & Genotoxicity of Andiroba Oil vs LLLT for Oral Mucositis in Hamsters

Oncotarget published this trending research paper in Volume 14, entitled, “Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels" by the researchers from Rudolf Schönheimer Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig 04103, Germany; Institute of Pathology, Medical Faculty, University of Leipzig, Leipzig 04103, Germany; Department of Dermatology, University Hospital Essen, University Duisburg-Essen, and German Cancer Consortium (DKTK) partner site Essen/Düsseldorf, Essen 45122, Germany.

DOI - https://doi.org/10.18632/oncotarget.28342

Correspondence to - Christina Kuhn - Christina.Kuhn@medizin.uni-leipzig.de 

Abstract

Overexpression of the dihydrolipoamide S-succinyltransferase (DLST) is associated with poor outcome in neuroblastoma patients and triple-negative breast cancer (TNBC) and specifically with the oxidative phosphorylation (OXPHOS) pathway. Inhibitors of OXPHOS were previously suggested as a potential therapeutic strategy for a subset of patients with high-risk neuroblastoma. Here, we tested if cell lines with DLST amplifications or high mRNA levels were associated with sensitivity to 250 drugs from the Genomics of Drug Sensitivity in Cancer (GDSC) dataset by comparing them to cell lines without these changes. DLST-altered cell lines were more sensitive to 7 approved drugs, among these obatoclax mesylate, a BCL2 inhibitor that reduces OXPHOS in human leukemia stem cells. Moreover, several protein kinase inhibitors were identified to be efficient in cell lines with DLST amplifications or high mRNA levels, suggesting a vulnerability of DLST-altered cell lines for drugs targeting the ERK/MAPK pathway. Furthermore, increased DLST expression in cell lines with driver mutations in KRAS supported this relationship. We therefore conclude that, in addition to OXPHOS, protein kinases could be potential targets of therapy in the presence of DLST amplifications or high mRNA levels. The new drug candidates proposed here could serve in experimental testing on drug efficacy in knock-in cell lines and DLST-activated tumors.

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Keywords - neuroblastoma, drug sensitivity, drug resistance, drug repurposing, DLST

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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Drugs Associated With Sensitivity of Cancer Cell Lines With DLST or High mRNA Levels

Oncotarget published this research paper in Volume 14, entitled, “Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001" by the researchers from the Research Development, Sutro Biopharma, South San Francisco, CA; Clinical Development, Sutro Biopharma, South San Francisco, CA.

DOI - https://doi.org/10.18632/oncotarget.28341

Correspondence to - Xiaofan Li - xli@sutrobio.com, and Arturo Molina - amolina@sutrobio.com

Abstract

Overexpression of CD74, a type II transmembrane glycoprotein involved in MHC class II antigen presentation, has been reported in many B-cell non-Hodgkin lymphomas (NHLs) and in multiple myeloma (MM). STRO-001 is a site-specific, predominantly single-species antibody-drug conjugate (ADC) that targets CD74 and has demonstrated efficacy in xenograft models of MM and tolerability in non-human primates. Here we report results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL. STRO-001 displayed nanomolar and sub-nanomolar cytotoxicity in 88% (15/17) of cancer cell lines tested. STRO-001 showed potent cytotoxicity on proliferating B cells while limited cytotoxicity was observed on naïve human B cells. A linear dose-response relationship was demonstrated in vivo for DLBCL models SU-DHL-6 and U2932. Tumor regression was induced at doses less than 5 mg/kg, while maximal activity with complete cures were observed starting at 10 mg/kg. In MCL Mino and Jeko-1 xenografts, STRO-001 starting at 3 mg/kg significantly prolonged survival or induced tumor regression, respectively, leading to tumor eradication in both models. In summary, high CD74 expression levels in tumors, nanomolar cellular potency, and significant anti-tumor in DLBCL and MCL xenograft models support the ongoing clinical study of STRO-001 in patients with B-cell NHL.
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Keywords - CD74, antibody-drug conjugate, non-Hodgkin lymphoma, xenograft models, STRO-001

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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Targeting CD74 in B-cell Non-Hodgkin Lymphoma With Antibody-Drug Conjugate STRO-001

CloudLIMS

CloudLIMS.com and Rajiv Gandhi Cancer Institute and Research Center, India organized a live webinar. The webinar provided valuable information about the challenges and opportunities faced by biorepositories and research labs by focusing on the role of biobanking in facilitating high-quality cancer research that helps enhance health and well-being.

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1. Why is Biobanking Imperative for the Progress of Clinical Research?
2. How to Overcome Challenges with Biobank Data Management?
3. Affordable Cloud-based Tools for Efficient Biobanking

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