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BUFFALO, NY- July 26, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 19, 2024, entitled, “Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.”
Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited.
In this new retrospective study, researchers Caroline Naomi Valdez, Gabriela Athziri Sánchez-Zuno, Lais Osmani, Wael Ibrahim, Anjela Galan, Antonietta Bacchiocchi, Ruth Halaban, Rajan P. Kulkarni, Insoo Kang, Richard Bucala, and Thuy Tran from Yale University, Oregon Health and Science University, Cancer Early Detection Advanced Research Center (CEDAR), and the Department of Veterans Affairs Portland Health Care System analyzed 97 patients treated at Yale for melanoma between 2002–2020.
“Our study significantly expands on prior work by De Azevedo et al. by encompassing a larger cohort of individuals, coupled with a comprehensive approach to defining high and low MIF and DDT expression.”
Bulk-RNA sequencing of patient tumor samples from the Skin Cancer SPORE Biorepository was used to evaluate for differential gene expression of MIF, DDT, CD74, and selected inflammatory markers, and gene expression was correlated with patient survival outcomes. Their findings revealed a strong correlation between MIF and DDT levels, with no statistically significant difference across common melanoma mutations and subtypes.
Improved survival was associated with lower MIF and DDT levels and higher CD74:MIF and CD74:DDT levels. High CD74:DDT and CD74:MIF levels were also associated with enrichment of infiltrating inflammatory cell markers. These data suggest DDT as a novel target in immune therapy. Dual MIF and DDT blockade may provide synergistic responses in patients with melanoma, irrespective of common mutations, and may overcome ICI resistance. These markers may also provide prognostic value for further biomarker development.
“Our study is the first to report survival findings in association with intratumor DDT expression and CD74:DDT expression level ratio. Thus, CD74:MIF and CD74:DDT expression ratio measurements offer promise as prognostic markers for survival outcomes and ICI response in patients with melanoma.”
DOI - https://doi.org/10.18632/oncotarget.28615
Correspondence to - Thuy Tran - [email protected]
Video short - https://www.youtube.com/watch?v=ULlzscn0PvQ
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Keywords - cancer, MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomics
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.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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In the ever-evolving quest for effective cancer treatments, researchers are continuously exploring innovative combinatorial approaches that exploit the vulnerabilities of malignant cells. In a new study, researchers Benigno C. Valdez, Apostolia M. Tsimberidou, Bin Yuan, Yago Nieto, Mehmet A. Baysal, Abhijit Chakraborty, Clark R. Andersen, and Borje S. Andersson from The University of Texas MD Anderson Cancer Center unveiled a promising synergistic strategy for combating pancreatic cancer (a cancer known for its resistance to conventional therapies).
On June 3, 2024, their research paper was published in Oncotarget’s Volume 15, entitled, “Synergistic cytotoxicity of histone deacetylase and poly-ADP ribose polymerase inhibitors and decitabine in pancreatic cancer cells: Implications for novel therapy.”
Full blog - https://www.oncotarget.org/2024/07/25/novel-triple-drug-combination-to-fight-pancreatic-cancer/
Research paper DOI - https://doi.org/10.18632/oncotarget.28588
Correspondence to - Apostolia M. Tsimberidou - [email protected]
Video short - https://www.youtube.com/watch?v=zwZVrAsdgE8
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Keywords - cancer, decitabine, HDAC inhibitors, pancreatic cancer, PARP inhibitors, synergistic cytotoxicity
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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Missing episodes?
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BUFFALO, NY- July 24, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 22, 2024, entitled, “Prevalence and impact of the KIT M541L variant in patients with mastocytosis.”
Activating mutations in KIT, particularly D816V, have been associated with mastocytosis. Additionally, expression of heterozygous KIT M541L has been primarily reported in patients with pediatric mastocytosis.
In this new study, researchers Luisa N. Dominguez Aldama, Eric Karlins, Xiaoping Sun, Daniel Veltri, Hirsh D. Komarow, Irina Maric, Dean D. Metcalfe, and Melody C. Carter from the National Institutes of Health examined the prevalence of this variant in pediatric and adult patients with mastocytosis (n = 100) compared to ancestry-matched 1000 genomes controls (n = 500) and patients with idiopathic anaphylaxis (n = 23). They then compared clinical symptoms and laboratory data on patients with systemic and cutaneous mastocytosis and bone marrow histopathology on a matched cohort with and without the KIT M541L variant.
“We found a significant association between KIT M541L genotype and the diagnosis of mastocytosis.”
Overall, the KIT M541L variant was identified in 19 individuals; the majority were diagnosed with systemic mastocytosis (89.4%) with an associated KIT D816V mutation. There were no significant differences in peripheral blood parameters between groups. Patients with mastocytosis carrying the KIT M541L variant did not demonstrate significant differences in symptomatology compared to a matched reference cohort (n = 13/81) without KIT M541L. In patients with idiopathic anaphylaxis, no significant associations were observed.
“To our knowledge, this is the first case/control study to show a significant genetic association with mastocytosis at the KIT M541L locus.”
DOI - https://doi.org/10.18632/oncotarget.28614
Correspondence to - Melody C. Carter - [email protected]
Video short - https://www.youtube.com/watch?v=zpiBbSfkTX4
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Keywords - cancer, mastocytosis, KIT M541L, KIT D816V, adults, pediatrics
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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BUFFALO, NY - July 22, 2024 – Oncotarget proudly welcomes new members to our esteemed Editorial Board, including our new Co-Editor-in-Chief, Dr. Wafik S. El-Deiry.
Joining Dr. El-Deiry on Oncotarget’s Editorial Board are Dr. Trever Bivona, Dr. Phillip Buckhaults, Dr. Fred Bunz, Dr. Jonathan Chernoff, Dr. Stephen G. Chun, Dr. Nathan Dolloff, Dr. Peiwen Fei, Dr. Justin D. Lathia, Dr. Bora Lim, Dr. Jia (Jenny) Liu, Dr. Hui-Wen Lo, Dr. Emil Lou, Dr. Anirban Maitra, Dr. Ruben A. Mesa, and Dr. Yashbir Singh.
To learn more about our outstanding members, please visit our Editorial Board page.
In celebration of the new additions to Oncotarget’s Editorial Board, we are excited to offer a special discount of 50% on all publication fees until the end of the year. This is our way of saying thank you to our supporters!
To learn about how to publish with Oncotarget, please visit our Editorial Policies page.
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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BUFFALO, NY- July 22, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 10, 2024, entitled, “Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma.”
Patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need.
In this new study, researchers Alexandra Jackovich, Barbara J. Gitlitz, Justin Wayne Wong Tiu-lim, Vinay Duddalwar, Kevin George King, Anthony B. El-Khoueiry, Jacob Stephen Thomas, Denice Tsao-Wei, David I. Quinn, Parkash S. Gill, and Jorge J. Nieva from Rutgers New Jersey Medical School and the University of Southern California conducted a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment.
“sEphB4-HSA in combination with pembrolizumab has a safety profile similar to what has been observed previously with no overlapping toxicity.”
The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome.
Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 – 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 45%) with 2 of these patients achieving a complete response (CR). The median PFS in HPV-negative/EphrinB2 positive patients was 3.2 months (95% CI 1.1, 7.3). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities.
“The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.”
DOI - https://doi.org/10.18632/oncotarget.28605
Correspondence to - Alexandra Jackovich - [email protected], and Jorge J. Nieva - [email protected]
Video short - https://www.youtube.com/watch?v=8SVmHYQigwA
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Keywords - cancer, EphrinB2, EphB4, HNSCC, pembrolizumab, HPV-negative
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.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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BUFFALO, NY- July 19, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on July 2, 2024, entitled, “DDX41 and its unique contribution to myeloid leukemogenesis.”
In this new editorial, researcher Hirotaka Matsui from the National Cancer Center Hospital in Tokyo, Japan, and Kumamoto University discusses myeloid neoplasms. Until the early 2000s, myeloid neoplasms attributable to genetic backgrounds were considered exceedingly rare, with notable exceptions limited to those arising as components of systemic syndromes such as Fanconi anemia and Li-Fraumeni syndrome. Historically, no hematopoietic-specific tumor syndromes had been identified until 1999, when RUNX1 was implicated as the causative gene for familial platelet disorder with a predisposition to acute myeloid leukemia (AML).
Subsequently, in 2004, CEBPA was recognized as another critical gene responsible for inherited AML. The subsequent advent and widespread application of comprehensive genetic analysis facilitated the identification of germline pathogenic variants in genes such as ANKRD26, ETV6, and GATA2 among patients with myeloid neoplasms that developed against a background of inherited thrombocytopenia or systemic disorders. It is now established that genetic predisposition is present in approximately 10% of myeloid neoplasms, underscoring the fact that myeloid neoplasms with a genetic background are by no means exceptional.
“Among these, myeloid neoplasms caused by DDX41 variants are particularly noteworthy due to their distinct disease phenotype and pathogenesis [2].”
DOI - https://doi.org/10.18632/oncotarget.28603
Correspondence to - Hirotaka Matsui - [email protected]
Video short - https://www.youtube.com/watch?v=AQXIdS1amhM
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Keywords - cancer, acute myeloid leukemia, DDX41, myelodysplastic neoplasms, myeloid neoplasms with germline predisposition, R-loop
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.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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BUFFALO, NY- July 17, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on July 2, 2024, entitled, “Using early on-treatment circulating tumor DNA measurements as response assessment in metastatic castration resistant prostate cancer.”
In this new editorial, researchers S.H. Tolmeijer, E. Boerrigter, N.P. Van Erp, and Niven Mehra from Radboud University Medical Center discuss metastatic castration resistant prostate cancer (mCRPC). mCRPC is lethal, but the number of life-prolonging systemic treatments available for mCRPC has expanded over the years. Real world data suggest that the most common first-line therapy for mCRPC was treatment with an androgen receptor pathway inhibitor (ARPI), being either enzalutamide or abiraterone, although more patients will nowadays receive ARPI and/or docetaxel already for hormone sensitive prostate cancer (HSPC).
Recent clinical trial data suggest potential benefit of adding poly-ADP ribose polymerase inhibitors (PARPi) or lutetium-117-prostate-specific membrane antigen (LuPSMA) to first-line mCRPC treatment with ARPIs in a subset of patients. As these different drug classes are associated with different toxicity profiles and significant costs, it is highly important to identify which patients experience durable benefit from monotherapy ARPI and which patients would potentially benefit from treatment intensification or therapy switch.
“Research by Tolmeijer et al. 2023, published in Clinical Cancer Research [13], suggests that the detection of circulating tumor DNA (ctDNA) at baseline and 4-weeks after treatment initiation can predict response durability to first-line ARPIs.”
DOI - https://doi.org/10.18632/oncotarget.28599
Correspondence to - Niven Mehra - [email protected]
Video short - https://www.youtube.com/watch?v=DTJ0vEnQ9SY
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Keywords - cancer, ctDNA, prostate cancer, liquid biopsy, biomarker, androgen receptor pathway inhibitors
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.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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BUFFALO, NY- July 16, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on June 20, 2024, entitled, “HER2-low and HER2-zero in breast cancer between prognosis, prediction and entity.”
In this new editorial, researchers Marcus Schmidt, Hans-Anton Lehr, and Katrin Almstedt from the University Medical Center of Johannes Gutenberg University discuss HER2 in breast cancer. HER2 is a well-established prognostic and predictive factor in breast cancer, which is associated with a poor prognosis but also offers the chance of improved survival when treated with targeted therapies based on the monoclonal antibody trastuzumab, both in advanced (hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.71 to 0.94, P = 0.004) and in early (HR 0.66, 95% CI 0.57 to 0.77, P < 0.00001) stages.
The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) defines HER2-positivity as either 3+ by immunohistochemistry (IHC) or 2+ with amplification by in situ hybridization (ISH). Yet, the vast majority of breast tumors are considered HER2- negative (IHC 0 or 1+ or 2+ without amplification) by these criteria, and it has until recently been accepted that HER2-negative tumors do not benefit from trastuzumab based therapy.
“Now, results of randomized trials with trastuzumab-based antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) have fundamentally challenged this long-held view.”
DOI - https://doi.org/10.18632/oncotarget.28598
Correspondence to - Marcus Schmidt - [email protected]
Video short - https://www.youtube.com/watch?v=4ROlLZo82uY
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Keywords - cancer, breast cancer, HER2, HER2-low, prognostic, predictive
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.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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BUFFALO, NY- July 15, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Comparison of FDG-PET/CT and CT for evaluation of tumor response to nivolumab plus ipilimumab combination therapy and prognosis prediction in patients with unresectable malignant pleural mesothelioma.”
Malignant pleural mesothelioma (MPM) is an aggressive neoplasm and affected patients have low survival rates. In this new retrospective study, researchers Kazuhiro Kitajima, Kozo Kuribayashi, Toshiyuki Minami, Hiroyuki Yokoyama, Akifumi Nakamura, Masaki Hashimoto, Takashi Kijima, Seiki Hasegawa, Hayato Kaida, and Koichiro Yamakado from Hyogo Medical University and Kindai University Faculty of Medicine examined the effectiveness of fluorodeoxyglucose positron emission tomography (FDG-PET) criteria, i.e., immunotherapy-modified PET response criteria in solid tumors (imPERCIST), with morphological computed tomography (CT) criteria, i.e., modified response evaluation criteria in solid tumors (mRECIST), to evaluate patients with unresectable MPM undergoing nivolumab plus ipilimumab combination therapy as first-line treatment regarding response and prognosis prediction.
“Results for malignant pleural mesothelioma (MPM) patients following first-line treatment with nivolumab plus ipilimumab obtained with immunotherapy-modified PERCIST (imPERCIST), shown by [18F] (FDG-PET/CT), and modified RECIST (mRECIST), shown by CT, were compared for response evaluation and prognosis prediction.”
Twenty-six patients (23 males, 3 females; median 73.5 years) with histologically proven MPM and no curative surgery received nivolumab plus ipilimumab combination therapy. FDG-PET/CT and diagnostic CT scanning at the baseline, and after 2–4 cycles (2 in three, 3 in 17, 4 in six patients) were performed. Therapeutic response findings evaluated using imPERCIST and mRECIST were compared. PFS and OS analyses were done using log-rank and Cox methods.
Results: imPERCIST indicated nine progressive metabolic disease (PMD), eight stable metabolic disease (SMD), four partial metabolic response (PMR), and five complete metabolic response (CMR) cases. mRECIST showed nine with progressive disease (PD), nine stable disease (SD), seven partial response (PR), and one complete response (CR). Although high concordance was noted (κ = 0.827), imPERCIST correctly judged a greater percentage with CMR (15.4%). Following a median 10.0 months, 15 patients showed progression and eight died from MPM. With both, progression-free survival (PFS) and overall survival (OS) were significantly longer in patients without progression (CMR/PMR/SMD, CR/PR/SD, respectively) as compared to PMD/PD patients (imPERCIST p < 0.0001 and p = 0.015, respectively; mRECIST p < 0.0001 and p = 0.015, respectively).
“For unresectable MPM patient examinations, FDG-PET and CT provide accurate findings for evaluating tumor response and also prognosis prediction following first-line nivolumab plus ipilimumab immunotherapy (approximately three cycles).”
DOI - https://doi.org/10.18632/oncotarget.28594
Correspondence to - Kazuhiro Kitajima - [email protected]
Video short - https://www.youtube.com/watch?v=7ZRTRwig60Y
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.
To learn more about Oncotarget, please visit https://www.oncotarget.com.
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Positron Emission Tomography (PET) combined with Computed Tomography (CT) is a powerful imaging modality used in oncology for diagnosis, staging, and treatment monitoring. However, one limitation of PET/CT is the need for accurate attenuation correction (AC) to account for tissue density variations. Traditionally, low-dose CT scans are used for AC, but these contribute to patient radiation exposure.
In a new study, researchers Kevin C. Ma, Esther Mena, Liza Lindenberg, Nathan S. Lay, Phillip Eclarinal, Deborah E. Citrin, Peter A. Pinto, Bradford J. Wood, William L. Dahut, James L. Gulley, Ravi A. Madan, Peter L. Choyke, Ismail Baris Turkbey, and Stephanie A. Harmon from the National Cancer Institute proposed an artificial intelligence (AI) tool to generate attenuation-corrected PET (AC-PET) images directly from non-attenuation-corrected PET (NAC-PET) images, reducing the reliance on CT scans. Their research paper was published in Oncotarget’s Volume 15 on May 7, 2024, entitled, “Deep learning-based whole-body PSMA PET/CT attenuation correction utilizing Pix-2-Pix GAN.”
Full blog - https://www.oncotarget.org/2024/07/11/ai-for-improved-pet-ct-attenuation-correction-in-prostate-cancer-imaging/
Paper DOI - https://doi.org/10.18632/oncotarget.28583
Correspondence to - Stephanie A. Harmon - [email protected]
Video short - https://www.youtube.com/watch?v=0mZItCB8AtI
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Keywords - cancer, deep learning, PSMA PET, attenuation correction
About Oncotarget
Oncotarget is an open-access, peer-reviewed journal that has published primarily oncology-focused research papers since 2010. These papers are available to readers (at no cost and free of subscription barriers) in a continuous publishing format at Oncotarget.com.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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BUFFALO, NY- July 10, 2024 – A new #editorial paper was #published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Targeting ABC transporters in PDAC – past, present, or future?”
In this new editorial, Cecilia Bergonzini, Elisa Giovannetti and Erik H.J. Danen from Leiden University discuss targeting ABC transporters in pancreatic ductal carcinoma (PDAC). Despite its lower incidence as compared to more common cancers such as lung or breast carcinomas, PDAC ranks as the third leading cause of cancer mortality in the US and the sixth worldwide. This is due to the fact that PDAC survival rates are among the lowest for cancer patients, around 13% in the US.
ATP-binding cassette (ABC) transporters represent a family of transmembrane proteins that, using the energy from ATP hydrolysis, extrude molecules from the cytoplasm to the exterior or into vesicles. Some of these transporters have been associated with resistance to a spectrum of structurally diverse chemotherapeutic drugs, earning them the name of multidrug resistance (MDR) pumps. One of the best-characterized ABC transporters is ABCB1 (MDR1). It is physiologically expressed in tissues such as kidney, liver, pancreas, intestine, the blood-brain barrier, and more, where it exerts a protective role, by extruding xenobiotics and potentially toxic molecules. Moreover, increased ABCB1 expression in tumors has been associated with poor prognosis.
“Paclitaxel is a bona fide substrate for ABCB1 [18] and ABCB1 has been implicated in paclitaxel and nab-paclitaxel resistance in multiple types of cancer [19, 20]. Could ABCB1 represent a therapeutic target in PDAC patients to suppress resistance against GnP? We have recently reported that ABCB1 can indeed play a critical role in paclitaxel resistance in PDAC cells [21].”
DOI - https://doi.org/10.18632/oncotarget.28597
Correspondence to - Erik H.J. Danen - [email protected]
Video short - https://www.youtube.com/watch?v=safa58X8NMY
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Keywords - cancer, PDAC, chemoresistance, ABCB1
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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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BUFFALO, NY- July 8, 2024 – A new research paper was published in Oncotarget's Volume 15 on July 2, 2024, entitled, “Regorafenib synergizes with TAS102 against multiple gastrointestinal cancers and overcomes cancer stemness, trifluridine-induced angiogenesis, ERK1/2 and STAT3 signaling regardless of KRAS or BRAF mutational status.”
Single-agent TAS102 (trifluridine/tipiracil) and regorafenib are FDA-approved treatments for metastatic colorectal cancer (mCRC). Researchers previously reported that regorafenib combined with a fluoropyrimidine can delay disease progression in clinical case reports of multidrug-resistant mCRC patients. In this new study, researchers Jun Zhang, Lanlan Zhou, Shuai Zhao, and Wafik S. El-Deiry from Fox Chase Cancer Center and Brown University hypothesized that the combination of TAS102 and regorafenib may be active in CRC and other gastrointestinal (GI) cancers and may in the future provide a treatment option for patients with advanced GI cancer.
“We investigated the therapeutic effect of TAS102 in combination with regorafenib in preclinical studies employing cell culture, colonosphere assays that enrich for cancer stem cells, and in vivo.”
TAS102 in combination with regorafenib has synergistic activity against multiple GI cancers in vitro including colorectal and gastric cancer, but not liver cancer cells. TAS102 inhibits colonosphere formation and this effect is potentiated by regorafenib. In vivo anti-tumor effects of TAS102 plus regorafenib appear to be due to anti-proliferative effects, necrosis and angiogenesis inhibition.
Growth inhibition by TAS102 plus regorafenib occurs in xenografted tumors regardless of p53, KRAS or BRAF mutations, although more potent tumor suppression was observed with wild-type p53. Regorafenib significantly inhibits TAS102-induced angiogenesis and microvessel density in xenografted tumors, as well inhibits TAS102-induced ERK1/2 activation regardless of RAS or BRAF status in vivo. TAS102 plus regorafenib is a synergistic drug combination in preclinical models of GI cancer, with regorafenib suppressing TAS102-induced increase in microvessel density and p-ERK as contributing mechanisms.
“The TAS102 plus regorafenib drug combination may be further tested in gastric and other GI cancers.”
DOI - https://doi.org/10.18632/oncotarget.28602
Correspondence to - Wafik S. El-Deiry - [email protected]
Video short - https://www.youtube.com/watch?v=tuEmJTkyyGQ
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Keywords - cancer, TAS102, regorafenib, ERK1/2, angiogenesis, microvessel density
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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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BUFFALO, NY- July 2, 2024 – A new editorial paper was published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Genomics has more to reveal.”
In this new editorial, researchers Laurène Fenwarth and Nicolas Duployez from the University of Lille and CHU Lille discuss molecular and cytogenetic analyses that are now used to identify mutations and structural variants defining distinct subtypes of acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS). These genetic considerations have become essential for risk stratification and the selection of appropriate treatments, including the use of allogeneic hematopoietic stem cell transplantation.
“Despite over 15 years of genomic research since the first publication of the AML genome and large studies like The Cancer Genome Atlas (TCGA) [2], around 15% of AML cases remained genetically unclassifiable with current knowledge.”
Notably, several studies in both adults and children identified a subset of AML without known initiating events but particularly enriched in FLT3- ITD and WT1 mutations, and normal karyotypes with an overall unfavorable prognosis. In 2021–2022, notably thanks to advancements in bioinformatic approaches and tools, recurrent somatic tandem duplications (TD) of a portion of the UBTF gene were identified in high-risk pediatric AML cases.
“With increased screenings of retrospective cohorts, the characteristics associated with this molecular alteration have since been confirmed. UBTF-TD are considered initiating events in leukemogenesis and define a distinct entity of myeloid malignancies.”
DOI - https://doi.org/10.18632/oncotarget.28596
Correspondence to - Nicolas Duployez - [email protected]
Video short - https://www.youtube.com/watch?v=WVY_ejhr7Fc
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Keywords - cancer, acute myeloid leukemia, genomics, UBTF
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BUFFALO, NY- June 26, 2024 – A new research perspective was published in Oncotarget's Volume 15 on June 20, 2024, entitled, “Starving cancer cells to enhance DNA damage and immunotherapy response.”
Prostate cancer (PCa) poses significant challenges in treatment, particularly when it progresses to a metastatic, castrate-resistant state. Conventional therapies, including chemotherapy, radiotherapy, and hormonal treatments, often fail due to toxicities, off-target effects, and acquired resistance. In this new research perspective, researchers Aashirwad Shahi and Dawit Kidane from Howard University define an alternative therapeutic strategy focusing on the metabolic vulnerabilities of PCa cells, specifically their reliance on non-essential amino acids such as cysteine.
“In this prospective, we will rise the driving questions and potential possibilities how amino acid depletion induced oxidative stress associated DNA damage exploited for DNA repair targeted and immune checkpoint blockade therapy [...].”
Using an engineered enzyme cyst(e)inase to deplete the cysteine/cystine can induce oxidative stress and DNA damage in cancer cells. This depletion elevates reactive oxygen species (ROS) levels, disrupts glutathione synthesis, and enhances DNA damage, leading to cancer cell death. The combinatorial use of cyst(e)inase with agents targeting antioxidant defenses, such as thioredoxins, further amplifies ROS accumulation and cytotoxicity in PCa cells.
“Overall, this perspective provides a compressive overview of the previous work on manipulating amino acid metabolism and redox balance modulate the efficacy of DNA repair-targeted and immune checkpoint blockade therapies in prostate cancer.”
DOI - https://doi.org/10.18632/oncotarget.28595
Correspondence to - Dawit Kidane - [email protected]
Video short - https://www.youtube.com/watch?v=Zrj24o_-b50
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Keywords - cancer, amino acid depletion, DNA damage, DNA repair, Immunotherapy, tumor immunity
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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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BUFFALO, NY- June 24, 2024 – A new editorial paper was published in Oncotarget's Volume 15 on June 14, 2024, entitled, “Leveraging gold nanostars for precision laser interstitial thermal therapy.”
In this new editorial, researchers Aden P. Haskell-Mendoza, Ethan S. Srinivasan, Tuan Vo-Dinh and Peter E. Fecci from Duke University discuss laser interstitial thermal therapy (LITT). Over the past decade, LITT has become an important tool for the neurosurgical treatment of a variety of intracranial pathologies, including focal epilepsies, vascular malformations, and central nervous system (CNS) tumors [1]. LITT involves the minimally invasive, stereotactically-guided placement of a laser catheter into a target lesion for subsequent thermal ablation via the delivery of infrared radiation, typically at wavelengths of 980–1064 nm [1, 2]. Following transfer of the patient to a scanner, real-time magnetic resonance (MR) thermometry is employed to track tissue hyperthermal ablation.
“For patients with primary and metastatic brain tumors who are suboptimal candidates for craniotomy due to clinical status, wound healing concerns, or tumor location, LITT represents a particularly favorable option for reducing tumor burden.”
However, successful ablation is limited by the (1) inability to precisely sculpt heat to cover or conform to large (typically, ≥3 cm) or irregular lesions, (2) the presence of various intracranial heat sinks, including cerebrospinal fluid (CSF) spaces and blood vessels, and (3) the sensitivity of uninvolved white and gray matter structures to inadvertent thermal damage [1–3].
“To aid in the performance of more efficient, conformal, and accordingly, safe ablations, we recently developed procedures for the use of gold nanostars (GNS, Figure 1) [2]."
DOI - https://doi.org/10.18632/oncotarget.28592
Correspondence to - Peter E. Fecci - [email protected]
Video short - https://www.youtube.com/watch?v=ZRMk0ZLjgxc
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Keywords - cancer, laser interstitial thermal therapy, gold nanostars, brain tumors, thermal ablation, immunotherapy
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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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Breast cancer immunotherapy has shown promise, but its clinical efficacy remains limited, especially for hormone receptor positive (HR+)/HER2-negative breast cancer. While immune checkpoint inhibitors combined with chemotherapy have benefitted some early-stage and metastatic triple-negative breast cancer patients, HR+/HER2-negative cases have seen fewer improvements.
Recent neoadjuvant trials indicate that early-stage HR+/HER2-negative breast cancers might respond better to immunotherapy strategies that amplify tumor-infiltrating lymphocytes (TILs) through dual PD-(L)1/CTLA-4 checkpoint inhibition before surgery and chemotherapy. This approach could enhance the immune response in the tumor microenvironment and improve outcomes for this challenging breast cancer subtype.
Increased TILs are associated with improved neoadjuvant chemotherapy (NACT) responses across breast cancer subtypes. Recently, researchers Haven R. Garber, Sreyashi Basu, Sonali Jindal, Zhong He, Khoi Chu, Akshara Singareeka Raghavendra, Clinton Yam, Lumarie Santiago, Beatriz E. Adrada, Padmanee Sharma, Elizabeth A. Mittendorf, and Jennifer K. Litton from the University of Texas MD Anderson Cancer Center, Brigham and Women’s Hospital, Dana-Farber Brigham Cancer Center, and Harvard Medical School hypothesized that amplifying TILs via dual checkpoint blockade would enhance the response to subsequent NACT in breast tumors.
Full blog - https://www.oncotarget.org/2024/06/20/impact-of-dual-immunotherapies-before-surgery-in-hr-her2-negative-breast-cancer/
Paper DOI -https://doi.org/10.18632/oncotarget.28567
Correspondence to - Haven R. Garber - [email protected]
Video short - https://www.youtube.com/watch?v=PHpndZJHB_c
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Keywords - cancer, breast cancer, ER positive, immunotherapy, neoadjuvant chemotherapy, tumor microenvironment
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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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BUFFALO, NY- June 19, 2024 – A new research paper was published in Oncotarget's Volume 15 on June 13, 2024, entitled, “Assessment of serum tumor markers CEA, CA-125, and CA19-9 as adjuncts in non-small cell lung cancer management.”
Conventional tumor markers may serve as adjuncts in non-small cell lung cancer (NSCLC) management. In this new study, researchers Scott Strum, Mark Vincent, Meghan Gipson, Eric McArthur, and Daniel Breadner from the Schulich School of Medicine and Dentistry, London Health Sciences Centre, and Royal College of Surgeons in Ireland analyzed whether three tumor markers (CEA, CA19-9, and CA-125) held associations with radiographic and clinical outcomes in NSCLC.
“The aim of this retrospective study was to provide additional evidence for the clinical use of conventional serum tumor markers CEA, CA19-9, and CA-125 in NSCLC management.”
It constituted a single-center study of NSCLC patients treated with systemic therapy at the London Regional Cancer Program. Serum tumor markers were analyzed for differences in radiographic responses (RECIST v1.1 or iRECIST), associations with clinical characteristics, and all-cause mortality. A total of 533 NSCLC patients were screened, of which 165 met inclusion criteria. A subset of 92 patients had paired tumor markers and radiographic scans.
From the latter population, median (IQR) fold-change from nadir to progression was 2.13 (IQR 1.24–3.02; p < 0.001) for CEA, 1.46 (IQR 1.13–2.18; p < 0.001) for CA19-9, and 1.53 (IQR 0.96–2.12; p < 0.001) for CA-125. Median (IQR) fold-change from baseline to radiographic response was 0.50 (IQR 0.27, 0.95; p < 0.001) for CEA, 1.08 (IQR 0.74, 1.61; p = 0.99) for CA19-9, and 0.47 (IQR 0.18, 1.26; p = 0.008) for CA-125.
“In conclusion, tumor markers are positioned to be used as adjunct tools in clinical decision making, especially for their associations with radiographic response (CEA/CA-125) or progression (CEA/CA-125/CA-19-9).”
DOI - https://doi.org/10.18632/oncotarget.28566
Correspondence to - Daniel Breadner - [email protected]
Video short - https://www.youtube.com/watch?v=8LO-Hn0fbrg
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Keywords - cancer, tumor marker, biomarker, lung cancer; NSCLC, translational research
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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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BUFFALO, NY- June 18, 2024 – A new #research perspective was #published in Oncotarget's Volume 15 on June 13, 2024, entitled, “When does a melanoma metastasize? Implications for management.”
In this new perspective, researchers John F. Thompson and Gabrielle J. Williams from The University of Sydney, Royal Prince Alfred Hospital, and the University of Western Australia discussed melanoma and timing treatment. Selecting which patients with clinically localized melanoma require treatment other than wide excision of the primary tumor is based on the risk or presence of metastatic disease. This in turn is linked to survival.
“Knowing if and when a melanoma is likely to metastasize is therefore of great importance.”
Several studies employing a range of different methodologies have suggested that many melanomas metastasize long before the primary lesion is diagnosed. Therefore, waiting for dissemination of metastatic disease to become evident before making systemic therapy available to these patients may be less effective than giving them post-operative adjuvant therapy initially if the metastatic risk is high. The identification of these high-risk patients will assist in selecting those to whom adjuvant systemic therapy can most appropriately be offered.
“Further studies are required to better identify high-risk patients whose primary melanoma is likely to have already metastasized.”
DOI - https://doi.org/10.18632/oncotarget.28591
Correspondence to - John F. Thompson - [email protected]
Video short - https://www.youtube.com/watch?v=1rOlvR5_6Sg
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Keywords - cancer, melanoma, metastasis, time, adjuvant systemic therapy, tumor doubling time
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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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BUFFALO, NY- June 11, 2024 – The Ride for Roswell is one of the nation’s largest cycling events—hosted by Roswell Park Comprehensive Cancer Center—to raise awareness and funds for cancer research and patient care. This charity bike ride, based out of Buffalo, New York, has brought people together for 28 years to celebrate cancer survivors, pay tribute to lives that have been lost, and to work together to support research and find a cure.
THE ORIGIN OF THE RIDE
The Ride for Roswell started in 1989 when Mitch Flynn, owner of the advertising agency Flynn & Friends, met Katherine Gioia. Katherine was a four-year-old patient battling a rare form of cancer. After Katherine’s death (less than a year after her diagnosis), Katherine’s mother, Anne Gioia, and aunt, Donna Gioia, founded the Roswell Park Alliance Foundation in her memory to raise money for cancer research and treatment. On June 29, 1996, Mitch and Alliance Foundation staff launched the first Ride for Roswell.
In the 28 years since then, thanks to over 135,000 riders and thousands of volunteers, the Ride for Roswell has raised over $72 million to fund cancer research. The event has become one of the largest charity rides in the United States.
THIS YEAR
This year, Ride Day is on Saturday, June 22, 2024, and will once again begin at the University at Buffalo North Campus. There are nine routes to choose from, ranging from five to 100 mile distances. All riders are encouraged to check in on the Thursday or Friday before Ride Day.
Learn more about The Ride, check in, and routes: www.rideforroswell.org/routes/
JOIN A TEAM: TEAM OPEN ACCESS
Impact Journals has been a part of this event since 2018 and continues to sponsor captain Sergei Kurenov’s peloton, Team Open Access. Team Open Access was named in honor of all open-source online medical journals, such as Oncotarget, Aging, Genes & Cancer, and Oncoscience. Sergei works at Roswell Park Comprehensive Cancer Center to create, develop, and implement innovative diagnostic and surgical pre-planning software used in cancer treatment. He has been riding in the event since 2016.
“I am proud to [say] that our team is supported again by open source cancer-related scientific journals: Oncotarget and Aging! Both of these journals publish high-impact research papers of general interest and biological significance in all fields of cancer research,” Sergei said.
There is still time to join Team Open Access in the Ride for Roswell. You can also support the team by giving a donation of any size. Any avenue of support you may choose to donate to the Ride for Roswell will make a difference and change lives.
“Finding a cure for cancer is something we are all incredibly passionate about, and we are so thankful and grateful for your support. Together, we can make a difference!” Sergei said. “Thank you so much for your donations, your support, and well wishes!”
Visit the Open Access team page to join or donate today:
give.roswellpark.org/site/TR/Specia…eam&fr_id=1940
For media requests, please contact [email protected]. -
In the relentless battle against non-small cell lung cancer (NSCLC) driven by epidermal growth factor receptor (EGFR) mutations, the development of resistance has long been a formidable obstacle. Historically, first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) like gefitinib, erlotinib, afatinib, and dacomitinib have faced a significant hurdle: the emergence of the T790M point mutation in approximately 50% of patients, rendering the tumor resistant to these therapies.
This resistance stems from a sobering reality – before treatment, a small subset of cancer cells already harbor the T790M mutation, conferring no selective advantage initially. However, once treatment commences, these rare mutated cells proliferate selectively, eventually dominating the tumor population and diminishing the effectiveness of first- and second-generation TKIs.
Full blog - https://www.oncotarget.org/2024/06/06/dr-blagosklonnys-strategy-from-osimertinib-to-preemptive-combinations/
Paper DOI - https://doi.org/10.18632/oncotarget.28569
Correspondence to - Mikhail V. Blagosklonny - [email protected], [email protected]
Video short - https://www.youtube.com/watch?v=UO5BGLIggTE
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Keywords - cancer, lung cancer, NSCLC, EGFR, resistance, afatinib, gefitinib, capmatinib
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.
Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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