Publications by authors named "Erkut Borazanci"

Background: Chemotherapy-induced peripheral neuropathy (CIPN), a common problem, can impair function and quality of life in patients, potentially limiting chemotherapy and adversely affecting outcomes.

Methods: This trial compared investigational hand therapy intervention (Investigational) compared with a traditional occupational therapy approach (Traditional) to prevent CIPN in patients with pancreatic cancer receiving gemcitabine and albumin-bound paclitaxel containing regimens.

Results: forty-nine patients were enrolled with 40 evaluable for statistical analysis (21 Investigational/19 Traditional).

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Background: Modulation of glucocorticoid receptor (GR) activity in tumor cells enhances chemotherapy efficacy. We evaluated the selective GR modulator relacorilant plus nab-paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) who had received at least 2 prior therapy lines.

Patients And Methods: In this open-label, single-arm, phase III study, patients received once-daily oral relacorilant (100 mg, titrated to 150 mg in 25 mg increments/cycle) and nab-paclitaxel (80 mg/m2) on days 1, 8, and 15 of 28-day cycles.

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The efficacy and safety of olaratumab plus nabpaclitaxel and gemcitabine in treatment-naïve participants with metastatic pancreatic ductal adenocarcinoma was evaluated. An initial phase 1b dose-escalation trial was conducted to determine the olaratumab dose for the phase 2 trial, a randomized, double-blind, placebo-controlled trial to compare overall survival (OS) in the olaratumab arm vs. placebo arms.

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Background: Pancreatic ductal adenocarcinoma (PDAC) accounts for 90% of all pancreatic carcinomas. Prognosis is poor with a worldwide five-year survival rate of 2-9%. Extent of metastasis is a prognostic factor.

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Background: Minnelide is a water-soluble prodrug of triptolide. Triptolide is an anticancer agent that targets cancer resistance through several mechanisms. Minnelide was evaluated in a phase I study in patients with advanced GI carcinomas to establish the safety, pharmacodynamic, antitumor activity, and recommended phase II dose (RP2D).

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Article Synopsis
  • Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, often diagnosed too late due to vague symptoms and lack of early detection methods; the study aimed to create a noninvasive circular RNA (circRNA)-based biomarker panel for earlier diagnosis.
  • Researchers identified 10 circRNA candidates linked to PDAC through a genome-wide discovery, narrowing it down to 5 for a liquid biopsy assay, which effectively distinguished between early and late disease stages with strong diagnostic accuracy.
  • Combining the circRNA panel with the cancer antigen 19-9 levels significantly improved early detection rates, achieving a high area under the curve (0.94) in validation tests,
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  • Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer that requires new treatment options, prompting research into its underlying mechanisms.
  • The study reveals a significant role of super-enhancers in regulating a cascade of RNA-binding proteins that enhance mRNA translation, promoting PDAC growth.
  • Targeting this cascade, specifically the protein arginine methyltransferase 1 (PRMT1), shows potential as a therapeutic strategy, particularly in Myc-high PDAC patients, leading to reduced tumor growth in experimental models.
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Malignant ascites is the accumulation of fluid in the peritoneum as a result of advanced cancer and often signifies the terminal phase of the disease. Management of malignant ascites remains a clinical challenge as symptom palliation is the current standard of cure. Previously, studies examining malignant ascites largely focused on ovarian and gastric cancer.

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  • The study aimed to evaluate the effectiveness, safety, and maximum tolerated dose (MTD) of palbociclib combined with nab-paclitaxel for treating advanced pancreatic ductal adenocarcinoma (PDAC).
  • Preclinical tests showed that this combination outperformed gemcitabine plus nab-paclitaxel in most cases, with some safety concerns leading to a maximum tolerated dose of palbociclib at 100 mg per cycle alongside nab-paclitaxel at 125 mg.
  • Although the treatment showed promise, the targeted 12-month survival rate of 65% was not achieved, indicating a need for further research.
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Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a poor prognosis. Despite high efficacy in multiple cancers, immunotherapy has had very little success in treating PDAC due to unfavorable characteristics such as low tumor mutational burden (TMB), low microsatellite instability (MSI), and non-immunogenic tumor microenvironment. Recently, however, there have been reports of rare PDAC cases with high TMB and DNA mismatch repair deficiency (dMMR) that have demonstrated positive response to immunotherapy.

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Recent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents patients treated at the HonorHealth Research Institute with a diagnosis of HRD MPC who received Mitomycin C (MMC) treatment from January 2013 until July 2018.

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Purpose: Tilsotolimod is an investigational synthetic Toll-like receptor 9 (TLR9) agonist that has demonstrated antitumor activity in preclinical models. The ILLUMINATE-101 phase I study explored the safety, dose, efficacy, and immune effects of intratumoral (it) tilsotolimod monotherapy in multiple solid tumors.

Patients And Methods: Patients with a diagnosis of refractory cancer not amenable to curative therapies received tilsotolimod in doses escalating from 8 to 32 mg into a single lesion at weeks 1, 2, 3, 5, 8, and 11.

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Article Synopsis
  • The study focuses on the increasing incidence of pancreatic ductal adenocarcinoma (PDAC), emphasizing the need for better early detection methods beyond the commonly used CA19-9 biomarker, which lacks sufficient sensitivity and specificity.
  • Researchers conducted a genomewide profiling of blood samples to identify exosomal microRNAs (miRNAs) as potential noninvasive biomarkers for early PDAC detection.
  • A total of 13 robust miRNA markers were identified that accurately distinguish PDAC patients from controls, particularly successful in detecting early-stage cases and improve diagnostic accuracy when combined with CA19-9 levels.
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Purpose: Chemotherapy resistance remains a major problem in many solid tumors, including breast, ovarian, and pancreatic cancer. Glucocorticoids are one potential driver of chemotherapy resistance as they can mediate tumor progression via induction of cell-survival pathways. We investigated whether combining the selective glucocorticoid receptor (GR) modulator relacorilant with taxanes can enhance antitumor activity.

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Purpose: There is a major shortage of reliable early detection methods for pancreatic cancer in high-risk groups. The focus of this preliminary study was to use Time Intensity-Density Curve (TIDC) and Marley Equation analyses, in conjunction with 3D volumetric and perfusion imaging to demonstrate their potential as imaging biomarkers to assist in the early detection of Pancreatic Ductal Adenocarcinoma (PDAC).

Experimental Designs: A quantitative retrospective and prospective study was done by analyzing multi-phase Computed Tomography (CT) images of 28 patients undergoing treatment at different stages of pancreatic adenocarcinoma using advanced 3D imaging software to identify the perfusion and radio density of tumors.

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Purpose: We present seven cases of advanced cancer patients who initially underwent tumor testing utilizing smaller, panel-based tests, followed by a variety of therapeutic treatments which ultimately resulted in progression of their disease. These cases demonstrate the value of utilizing WES/RNA seq and characterization following disease progression in these patients and the determination of clinically targetable alterations as well as acquired resistance mutations.

Materials And Methods: All patients are part of an IRB approved observational study.

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Purpose: DNA methylation alterations have emerged as front-runners in cell-free DNA (cfDNA) biomarker development. However, much effort to date has focused on single cancers. In this context, gastrointestinal (GI) cancers constitute the second leading cause of cancer-related deaths worldwide; yet there is no blood-based assay for the early detection and population screening of GI cancers.

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  • The study investigates the effects of combining motixafortide, pembrolizumab, and chemotherapy on patients with metastatic pancreatic ductal adenocarcinoma (PDAC) who have not responded to previous gemcitabine-based treatment.
  • A total of 43 patients participated, showing a 21.1% objective response rate and a median progression-free survival of 3.8 months, indicating some effectiveness of the treatment.
  • The combination therapy was found to be safe, with low instances of severe side effects, demonstrating promise for a challenging cancer type that typically has limited treatment options.
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  • A first-in-human dose-escalation study was performed to assess the safety and effectiveness of the oral FASN inhibitor TVB-2640, both alone and combined with taxane chemotherapy, in patients with advanced metastatic solid tumors.
  • The study, conducted at 11 sites in the US and UK, involved 136 patients, with the maximum tolerated dose established at 100 mg/m, and key side effects included skin and ocular issues, as well as common treatment-emergent adverse events like alopecia and fatigue.
  • The results indicated a disease control rate of 42% for TVB-2640 monotherapy, with some serious adverse events, including one drug-related fatality, prompting ongoing safety assessments and targeting of cancer metabolism issues
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Background: We assessed the safety, efficacy, and pharmacokinetics of the transforming growth factor beta (TGFβ) receptor inhibitor galunisertib co-administered with the anti-programmed death-ligand 1 (PD-L1) antibody durvalumab in recurrent/refractory metastatic pancreatic cancer previously treated with ≤2 systemic regimens.

Methods: This was a two-part, single-arm, multinational, phase Ib study. In a dose-finding phase, escalating oral doses of galunisertib were co-administered on days 1-14 with fixed-dose intravenous durvalumab 1500 mg on day 1 every 4 weeks (Q4W), followed by an expansion cohort phase.

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Background: Solid tumors such as pancreatic ductal adenocarcinoma (PDAC) comprise not just tumor cells but also a microenvironment with which the tumor cells constantly interact. Detailed characterization of the cellular composition of the tumor microenvironment is critical to the understanding of the disease and treatment of the patient. Single-cell transcriptomics has been used to study the cellular composition of different solid tumor types including PDAC.

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Purpose: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent preclinical activity against G2032R solvent-front mutation among others. We report the first-in-human U.S.

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Purpose: Metformin combined with the mTOR inhibitor rapamycin showed potential synergistic anti-tumor activity in preclinical studies in pancreatic ductal adenocarcinoma (PDA). This phase 1b study (NCT02048384) was conducted to evaluate the feasibility and activity of metformin +/- rapamycin in the maintenance setting for unselected patients with metastatic PDA (mPDA) treated with chemotherapy.

Materials And Methods: Eligible patients with stable or responding mPDA after ≥ 6 months on chemotherapy were randomized 1:1 to metformin alone (Arm A) or with rapamycin (Arm B), stratified by prior treatment with FOLFIRINOX.

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