Oncotarget

A new research paper was published in Oncotarget's Volume 14 on January 12, 2023, 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.”

The oral mucositis is a mucosal alteration that usually arises from oncological treatments, such as chemotherapy, and it is characterized as an inflammatory process. In this new study, researchers Jessica T. Gomes, Ana Márcia V. Wanzeler, Sergio M.A. Júnior, Rosa Helena F. Chaves Soares, Carolina P. de Oliveira, Emanuelle de M. Rodrigues, Bruno M. Soares, Diego D.F.A. Alcantara, Rommel M.R. Burbano, and Fabrício M. Tuji from Federal University of Pará and the University Center of Pará aimed to demonstrate the chromatographic constitution of Andiroba oil, while comparing and evaluating Andiroba oil and laser scarring efficiency in treatments of oral mucositis in hamsters.

“The low-level laser therapy (LLLT) is the best standard treatment and the most efficient method in treating OM. Similarly, the andiroba oil presents great potential for the treatment of inflammatory diseases. Thus, this study aims to evaluate the healing and toxicological effects of andiroba oil, compared to the LLLT outcomes, observing if andiroba presents a similar/higher potential than the LLLT.”

The animals were submitted to 5-Fluorouracil. Included in the study were total of 122 animals that were 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 analyzed 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.”

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

Correspondence to: Diego D.F.A. Alcantara - [email protected]

Video: https://www.youtube.com/watch?v=wMwTGk7-VGU

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

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Listen to a blog summary of a trending research paper published in Volume 14 of Oncotarget: "Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels."

____________________________________________________

Dihydrolipoamide S-succinyltransferase (DLST) is a crucial gene/protein/enzyme involved in the oxidative phosphorylation (OXPHOS) pathway and cellular energy production. Recent studies have demonstrated that, in neuroblastoma and triple-negative breast cancer (TNBC), increased expression of DLST is associated with increased tumor aggression and a poor disease prognosis. Researchers also found that, in leukemia and TNBC cell lines, the knockdown of DLST leads to apoptosis. These findings suggest that neuroblastoma and TNBC may benefit from DLST-inhibiting cancer therapy.

In light of this evidence, researchers Christina Kuhn, Myriam Boeschen, Manuel Philip, Torsten Schöneberg, Doreen Thor, and Susanne Horn from the University of Leipzig, University Duisburg-Essen and the German Cancer Consortium investigated approved drugs that target DLST-activated tumors. In their recent study, the team used data from the Genomics of Drug Sensitivity in Cancer (GDSC) project to identify new drug candidates for the treatment of DLST-activated tumors. On January 12, 2023, their research paper was published in Oncotarget’s Volume 14, entitled, “Candidate drugs associated with sensitivity of cancer cell lines with DLST amplification or high mRNA levels.”

“With the advent of complex genetic datasets of roughly 1000 cell lines in the Cancer Cell Line Encyclopedia (CCLE) and on drug resistance in the Genomics of Drug Sensitivity in Cancer project (GDSC), analyses of drug sensitivity have become possible on a larger scale [6, 7].”

Full blog - https://www.oncotarget.org/2023/01/19/researchers-identify-new-drug-candidates-to-treat-dlst-tumors/

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

Correspondence to - Christina Kuhn - [email protected]

Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.28342

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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A new research paper was published in Oncotarget's Volume 14 on January 12, 2023, entitled, “Targeting CD74 in B-cell non-Hodgkin lymphoma with the antibody-drug conjugate STRO-001.”

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.

In this new study, researchers Xiaofan Li, Cristina Abrahams, Abigail Yu, Millicent Embry, Robert Henningsen, Venita DeAlmeida, Shannon Matheny, Toni Kline, Alice Yam, Ryan Stafford, Trevor Hallam, Mark Lupher, and Arturo Molina from Sutro Biopharma reported the results of preclinical studies designed to elucidate the potential role of STRO-001 in B-cell NHL.

“In order to explore the potential of STRO-001 in NHL, in the present study we investigated CD74 expression in cell types found in bone marrow, evaluated its cytotoxicity in NHL cell lines, and assessed its antitumor efficacy and toxicity in xenograft models of 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.”

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

Correspondence to: Xiaofan Li - [email protected], Arturo Molina - [email protected]

Keywords: CD74, antibody-drug conjugate, non-Hodgkin lymphoma, xenograft models, STRO-001

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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A new research paper was published in Oncotarget’s Volume 13 on December 29, 2022, entitled, “Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore.”

Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ12,14-prostamide J2 (15d-PMJ2) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells. Additionally, 15d-PMJ2 reduces melanoma growth in vivo.

To assess the chemotherapeutic potential of 15d-PMJ2, researchers Daniel A. Ladin, Margaret M. Nelson, Estefani Cota, Catherine Colonna, Colin Burns, Jacques Robidoux, Kelsey H. Fisher-Wellman, and Rukiyah Van Dross-Anderson from East Carolina University and University of North Carolina at Chapel Hill sought to uncover molecular pathways by which 15d-PMJ2 exerts its antitumor activity.

B16F10 melanoma and JWF2 squamous cell carcinoma cell lines were cultured in the presence of pharmacological agents that prevent ER or oxidative stress as well as Ca2+ channel blockers to identify mechanisms of 15d-PMJ2 cell death.

“Our data demonstrated the ER stress protein, PERK, was required for 15d-PMJ2-induced death.”

PERK activation triggered the release of ER-resident Ca2+ through an IP3R sensitive pathway. Increased calcium mobilization led to mitochondrial Ca2+ overload followed by mitochondrial permeability transition pore (mPTP) opening and the deterioration of mitochondrial respiration. Finally, the researchers showed that the electrophilic double bond located within the cyclopentenone ring of 15d-PMJ2 was required for its activity.

“The present study identifies PERK/IP3R/mPTP signaling as a mechanism of 15d-PMJ2 antitumor activity.”

DOI: https://doi.org/10.18632/oncotarget.28334

Correspondence to: Rukiyah Van Dross-Anderson - [email protected]

Keywords: calcium, mitochondrial respiration, endoplasmic reticulum stress, cancer, prostamide

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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A new research paper was published in Oncotarget's Volume 13 on December 29, 2022, entitled, “Impact of Covid-19 on the management of patients with metastatic melanoma.”

The Covid-19 pandemic created new uncertainties in the management of metastatic melanoma patients. In particular, the impact of immunotherapy, targeted therapy or chemotherapy on the risk of Sars-CoV-2 infection and severity was debated.

In this study, researchers Michèle Welti, Phil F. Cheng, Joanna Mangana, Mitchell P. Levesque, Reinhard Dummer, and Laurence Imhof from University Hospital Zurich, University of Zurich and ETH Zurich analyzed all patients with metastatic melanoma receiving therapy at the Department of Dermatology at the University Hospital Zürich who developed Covid-19 between February 2020 and February 2022.

“We retrospectively collected demographic data, cancer-specific parameters, melanoma treatment regimen, comorbidities and Covid-19-specific parameters in these patients.”

Of the 350 patients with metastatic melanoma, 25 had Covid-19. The median age at the time of Covid-19 diagnosis was 66 years (range 36–86), 10 patients were female and 15 patients were male. The treatment regimen during infection was immunotherapy in 12 cases, followed by targeted therapy (n = 8), chemotherapy (n = 2) and TVEC injections, follow-up and palliative therapy in 1 case each.

The severity was mild in 17 patients and 8 had a moderate to critical course. Patients with a severe Covid-19 course were often older and had more comorbidities than patients with a mild infection. Many of the patients had a mild Covid-19 course despite having metastatic melanoma and systemic therapy.

“We therefore recommend continuing systemic therapy whenever possible, even in such exceptional situations as the Covid-19 pandemic.”

DOI: https://doi.org/10.18632/oncotarget.28333

Correspondence to: Michèle Welti - [email protected]

Keywords: metastatic melanoma, Covid-19, Sars-CoV-2, immunotherapy, targeted therapy

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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A new research paper was published in Oncotarget's Volume 13 on December 20, 2022, entitled, “Resistance of MMTV-NeuT/ATTAC mice to anti-PD-1 immune checkpoint therapy is associated with macrophage infiltration and Wnt pathway expression.”

One of the central challenges for cancer therapy is the identification of factors in the tumor microenvironment that increase tumor progression and immune tolerance. In breast cancer, fibrosis is a histopathologic criterion for invasive cancer and poor survival that results from inflammatory factors and remodeling of the extracellular matrix to produce an immune-tolerant microenvironment.

In this new study, researchers Hongyan Yuan, Lu Jin, Handan Xiang, Anannya Bhattacharya, Philip E. Brandish, Gretchen Baltus, Alexander Tong, Changyan Zhou, and Robert I. Glazer from Georgetown University Medical Center, Merck Research Institute and Bicycle Therapeutics aimed to determine whether tolerance is associated with the immune checkpoint, Programmed Cell Death 1 (PD-1). A conditional model of mammary fibrosis recently developed by this team, NeuT/ATTAC mice, were administered a murine-specific anti-PD-1 mAb related to pembrolizumab. The researchers monitored drug response by tumor development, imaging mass cytometry, immunohistochemistry, and tumor gene expression by RNAseq.

“Utilizing this more stringent tumor model to test its susceptibility to anti-PD-1 immunotherapy, we report the signaling processes associated with its lack of responsiveness.”

Tumor progression in NeuT/ATTAC mice was unaffected by weekly injection of anti-PD-1 over four months. Insensitivity to anti-PD-1 was associated with several processes, including increased tumor-associated macrophages (TAM), epithelial to mesenchymal transition (EMT), fibroblast proliferation, an enhanced extracellular matrix and the Wnt signaling pathway, including increased expression of Fzd5, Wnt5a, Vimentin, Mmp3, Col2a1, and Tgfβ1. These results suggest potential therapeutic avenues that may enhance PD-1 immune checkpoint sensitivity, including the use of tumor microenvironment targeted agents and Wnt pathway inhibitors.

“Overall, the immune tolerant TME in NeuT/ATTAC mice was associated with tumor-infiltrating macrophages, Foxp3+/PD-1- Treg cells as well as upregulation of the Wnt signaling pathway, which may provide further insights into the therapeutic options that may enhance immune checkpoint therapy.”

DOI: https://doi.org/10.18632/oncotarget.28330

Correspondence to: Robert I. Glazer - [email protected]

Keywords: PD-1, NeuT, Wnt, macrophages, mammary tumorigenesis

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Listen to a blog summary of a trending research paper published by Oncotarget: "Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model."

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The average age of patients with acute myeloid leukemia (AML) is 67 years old. Older adults generally have a lower tolerance for treatments that exhibit high off-target toxicity. Additionally, chemotherapy-relapsed or -refractory (R/R) AML patients are often at an advanced stage of disease and are therefore more likely to have comorbidities that may reduce their tolerance for harsh treatments.

Thus, pharmaceutical AML drugs with high efficacy and low toxicity are in high demand. Antibody drug conjugates (ADCs) are emerging as promising therapeutic approaches to more safely treat hematological malignancies by reducing side effects. ADCs are designed to decrease damage to healthy tissues by specifically targeting tumor-associated antigens attached to cancer cells.

“Antibody drug conjugates (ADC) are one of the modalities that aims to dissociate drug efficacy from toxicity. ADC consists of three components: antibody specific for tumor associated antigen, drug linker and cytotoxic payload.”

ASTELLAS PHARMA

Recently, researchers from Astellas Pharma Inc. (a pharmaceutical company in Japan) developed ASP1235—a novel ADC that targets Fms-like tyrosine kinase 3 (FLT3). In more than 90% of AML patients, FLT3 is overexpressed on leukemic blasts. ASP1235 is designed to target FLT3-positive leukemia cells and deliver the cytotoxic drug payload to these cells. However, this drug alone was found to have only a mild effect on AML cells, prompting researchers to assess the efficacy of ASP1235 in combination with other drugs.

In a new study, Astellas Pharma researchers Hirofumi Tsuzuki, Tatsuya Kawase, Taisuke Nakazawa, Masamichi Mori, and Taku Yoshida investigated the efficacy of ASP1235 combined with venetoclax (an anti-apoptotic agent) and azacitidine (a DNA methyltransferase inhibitor) in an experimental mouse model of AML. Their research paper was published in Oncotarget on December 20, 2022, and entitled, “Anti-tumor effect of antibody drug conjugate ASP1235 targeting Fms-like tyrosine kinase 3 with venetoclax plus azacitidine in an acute myeloid leukemia xenograft mouse model.”

Full blog: https://www.oncotarget.org/2023/01/04/novel-antibody-drug-conjugate-improves-murine-acute-myeloid-leukemia/

DOI: https://doi.org/10.18632/oncotarget.28331

Corresponding author: Hirofumi Tsuzuki - [email protected]

Keywords: acute myeloid leukemia (AML), ASP1235, antibody drug conjugate (ADC), venetoclax, azacitidine

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 13 on December 17, 2022, entitled, “Serum microRNAs as new criteria for referral to early palliative care services in treatment-naïve advanced cancer patients.”

A major obstacle to the implementation of early palliative care (EPC) is the lack of objective criteria for referral to EPC. Circulating microRNAs (miRNAs) have been recognized as promising biomarkers.

In the current study, researchers Tomofumi Miura, Shuichi Mitsunaga, Juntaro Matsuzaki, Satoko Takizawa, Ken Kato, Atsushi Ochiai, and Takahiro Ochiya from National Cancer Center Research Institute, National Cancer Center Hospital, Keio University, Toray Industries, Inc., and Tokyo Medical University investigated objective definitions for referral to EPC using microRNA. A total of 178 serum samples were obtained from patients with lung, gastrointestinal, colorectal, bile duct, pancreas, and bladder cancers who were treatment-naïve and received chemotherapy between January 2011 and December 2013 at National Cancer Center Hospital East.

“The aim of the present study was to develop predictive models using serum miRNAs for patients who [were] admitted to a PCU [palliative care unit] ≤6 months after starting anti-tumor treatment.”

The team investigated expression levels of miRNAs using microarrays. The primary outcome was prediction of admission to a palliative care unit ≤6 months after first visit. Diagnostic models using clinical characteristics, miRNAs and combinations of both were constructed. The miRNA models were constructed using 6 miRNA levels.

The best areas under the receiver operating characteristic curve (AUCs) of the clinical model was 0.741, while the average AUCs of miRNA-based models and combination models were 0.769 and 0.806, respectively. Combination models showed higher AUCs than the clinical model (p < 0.023). The researchers assert that the present combination models might offer new objective definitions for referral to EPC and thus contribute to real-world implementation of EPC.

“The present study developed a predictive model using miRNA for patients admitted to a PCU ≤6 months after starting anti-tumor treatment. The present models might offer objective criteria for oncologists to facilitate the referral of patients to the EPC.”

DOI: https://doi.org/10.18632/oncotarget.28327

Correspondence to: Shuichi Mitsunaga - [email protected]

Keywords: microRNA, early palliative care, integration, cancer, referral

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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A new research paper was published in Oncotarget's Volume 13 on December 17, 2022, entitled, “The role of pyrethroid derivatives in autophagy and apoptosis crosstalk signaling and potential risk for malignancies.”

Pyrethroids are extensively used insecticides by virtue of insecticidal activity potential in Asia, especially India, and in different nations worldwide to counter mosquitoes and insects for household or agricultural needs. The continuous widespread and uncontrolled use of pyrethroids and its derivatives have influenced multiple deleterious effects resulting in a potential risk factor causing damage to organ systems. Allethrin and prallethrin are extensively used, yet their influences on human primary cells are very limited or under-reported. The potential mechanisms by which allethrin and prallethrin modulates human primary cells, especially the molecular mechanisms or interconnectivity of autophagy-apoptosis, their clinical relevance in human subjects or patients are not well defined.

In the current study, researchers Jyothi Puvula, Narendra Maddu, Nagajothi Gutam, Asha Parimal, and Raghavendra B. Pongali from Sri Krishnadevaraya University, Queen Mary’s College, Manipal University, and National Institute of Biomedical Genomics furnished the evidence that both allethrin and prallethrin user samples significantly induced Ccl2 mRNA expression, increased amount of reactive oxygen intermediate, inhibited membrane bound enzymes and altered membrane fluidity.

Pyrethroid derivative users had induced levels of lipid peroxidation and induced binding activities of transcription factors(tfs) like CEBP-β and NF-AT. Pyrethroid derivatives induced autophagy, elicited intracellular Ca2+ concentration, calcineurin and regulated proapoptotic genes, DAPK1, Bim.

“Our current study presumably comprises the initial investigation of a very new mechanism of pyrethroid derivatives-moderated programmed cell death in various cell sets or types, like human primary cells where-in this is a late event, is documented.”

Hence, the current research study might be significant in the various pyrethroid derivatives-allied hematological-related cancers and immunosuppressant or auto-immune disorders. In the foremost instance, the researchers present data stating that pyrethroid derivatives induces multiple cell signaling cascades, like CEBP-β, NF-AT, ERK and MAPK having a role in autophagy thereby; synchronously effectively impact on the apoptosis, therefore causing hematological tumors and toxic or immune related disorders.

“Overall this current study might facilitate to formulate therapeutics or intervention targets that might serve to decrease the effect or impact of pyrethroids derivatives by targeting the signaling cascade that serves to minimize the modulation of autophagy mediated apoptosis.”

DOI: https://doi.org/10.18632/oncotarget.28328

Correspondence to: Raghavendra B. Pongali - [email protected]

Keywords: allethrin, prallethrin, autophagy, apoptosis, Ccl2

About Oncotarget:

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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A new research paper was published in Oncotarget's Volume 13 on December 6, 2022, entitled, “Plasma growth hormone is a potential biomarker of response to atezolizumab and bevacizumab in advanced hepatocellular carcinoma patients.”

Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment.

In this new study, researchers Yehia I. Mohamed, Dan G. Duda, Muhammad O. Awiwi, Sunyoung S. Lee, Lina Altameemi, Lianchun Xiao, Jeffrey S. Morris, Robert A. Wolff, Khaled M. Elsayes, Rikita I. Hatia, Aliya Qayyum, Shadi M. Chamseddine, Asif Rashid, James C. Yao, Armeen Mahvash, Manal M. Hassan, Hesham M. Amin, and Ahmed Omar Kaseb from MD Anderson Cancer Center, Massachusetts General Hospital, Harvard Medical School, Michigan State University, University of Pennsylvania, and Perelman School of Medicine investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev).

“The present study was designed to investigate the association between GH levels and overall survivals (OS) and progression free survival (PFS) in HCC patients treated with current standard, atezolizumab plus bevacizumab.”

The study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and used to stratify the HCC patients into GH-high and GH-low groups (the cutoff normal GH levels in women and men are ≤3.7 μg/L and ≤0.9 μg/L, respectively). The Kaplan-Meier method was used to calculate median OS and PFS and Log rank test was used to compare survival outcomes between GH-high and -low groups.

Thirty-seven patients were included in this analysis, of whom 31 were males and 6 females, with a median age of 67 years (range: 37–80). At the time of the analysis, the one-year survival rate was 70% (95% CI: 0.51, 0.96) among GH low patients and 33% (95% CI: 0.16, 0.67) among GH high patients. OS was significantly superior in GH-low compared to GH-high patients (median OS: 18.9 vs. 9.3 months; p = 0.014). PFS showed a non-significant trend in favor of GH-low patients compared to the GH-high group (median PFS: 6.6 vs. 2.9 months; p = 0.053).

“Plasma GH is a biomarker candidate for predicting treatment outcomes in advanced HCC patients treated with Atezo/Bev. This finding should be further validated in larger randomized clinical trials in advanced HCC patients.”

DOI: https://doi.org/10.18632/oncotarget.28322

Correspondence to: Ahmed Omar Kaseb - [email protected]

Keywords: growth hormone, hepatocellular carcinoma, immunotherapy, atezolizumab, bevacizumab

About Oncotarget:

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