Oncotarget

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]

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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]

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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.

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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

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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

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 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]

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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]

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Keywords - cancer, amino acid depletion, DNA damage, DNA repair, Immunotherapy, tumor immunity

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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.

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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