Phase 1 Trial of TTI-101, a First-in-Class Oral Inhibitor of STAT3 in Patients with Advanced Solid Tumors.

Purpose: Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is essential for the survival and immune sequestration of cancer cells. We conducted a phase 1 study of TTI‑101, a first-in-class, selective small-molecule inhibitor of STAT3, in patients with advanced metastatic cancer.

Patients And Methods: Patients were treated with TTI-101 orally twice daily in 28-day cycles at 4 dose levels (DLs): 3.

A Novel Triplet of Alisertib Plus Ibrutinib Plus Rituximab Is Active in Mantle Cell Lymphoma.

: Aurora (AK) A/B are oncogenic mitotic kinases that when over-expressed are poor prognostic markers in mantle cell lymphoma (MCL). : Alisertib, an AK-A inhibitor, has anti-tumor activity in relapsed/refractory (r/r) MCL patients. We evaluated alisertib plus ibrutinib in MCL to abrogate ibrutinib resistance.

Mucosal Melanoma: An Overview of Recent Therapies.

Mucosal Melanoma (MM) is an aggressive disease that is distinct from cutaneous melanoma risk in risk factors, prognosis, and treatment. Surgical treatment is currently the treatment of choice for localized disease; however, the recurrence rate is common. For advanced or metastatic disease, immunotherapy with PD-1 inhibitors and anti-CTLA is generally first-line treatment, however the overall responses to immunotherapy in MM are often lower and less robust when compared to that observed in cutaneous melanoma.

Low-Dose Eribulin Promotes NK Cell-Mediated Therapeutic Efficacy in Bladder Cancer.

Unlabelled: Despite its immunogenic nature, bladder cancer (BCa) responds sub-optimally to FDA-approved immunotherapy.

Background/objectives: We have previously shown that natural killer (NK) cells are major contributors to overall patient survival in BCa. In our efforts to identify clinically approved agents that enhance NK cell activation, we identified eribulin, a microtubule destabilizer primarily used in breast cancer.

CELF2 promotes tau exon 10 inclusion via hinge domain-mediated nuclear condensation.

Alternative splicing is a fundamental process that contributes to the functional diversity and complexity of proteins. The regulation of each alternative splicing event involves the coordinated action of multiple RNA-binding proteins, creating a diverse array of alternatively spliced products. Dysregulation of alternative splicing is associated with various diseases, including neurodegeneration.

Colibactin Exerts Androgen-dependent and -independent Effects on Prostate Cancer.

Background And Objective: The etiology of prostate cancer (PC) is multifactorial and poorly understood. It has been suggested that colibactin-producing Escherichia coli positive for the pathogenicity island pks (pks) initiate cancers via induction of genomic instability. In PC, androgens promote oncogenic translocations.

An Introductory Course on Geriatric Oncology.

Introduction: The need to train oncologists to address the complexities of the aging population has been a focus of educational initiatives and strategies since the 1980s. However, large gaps in the dissemination and implementation of geriatric oncology curricula are still present. Currently, few resources exist for oncology training programs to implement a formal geriatric oncology curriculum.

HADHA Regulates Respiratory Complex Assembly and Couples FAO and OXPHOS.

Oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) are key bioenergetics pathways. The machineries for both processes are localized in mitochondria. Secondary OXPHOS defects have been documented in patients with primary FAO deficiencies, and vice versa.

Tumour-intrinsic PDL1 signals regulate the Chk2 DNA damage response in cancer cells and mediate resistance to Chk1 inhibitors.

Background: Aside from the canonical role of PDL1 as a tumour surface-expressed immune checkpoint molecule, tumour-intrinsic PDL1 signals regulate non-canonical immunopathological pathways mediating treatment resistance whose significance, mechanisms, and therapeutic targeting remain incompletely understood. Recent reports implicate tumour-intrinsic PDL1 signals in the DNA damage response (DDR), including promoting homologous recombination DNA damage repair and mRNA stability of DDR proteins, but many mechanistic details remain undefined.

Methods: We genetically depleted PDL1 from transplantable mouse and human cancer cell lines to understand consequences of tumour-intrinsic PDL1 signals in the DNA damage response.

Radiation target nomenclature for lymphoma trials: consensus recommendations from the National Clinical Trials Network groups.

Contemporary lymphoma radiation target volumes that rely on post-systemic therapy imaging do not have standardised nomenclature. A forum of radiation oncology lymphoma leaders from the National Clinical Trials Network groups (NRG Oncology, Children's Oncology Group, SWOG Cancer Research Network, Alliance for Clinical Trials in Oncology, Eastern Cooperative Oncology Group-American College of Radiology Imaging Network Cancer Research Group, and the Canadian Cancer Trials Group) was convened and established standardised nomenclature for these volumes in the autumn of 2024. Involved-site radiotherapy includes the full cranial-caudal extent of prechemotherapy disease and takes into account axial anatomical changes only.

Barriers to Offering Organ Preservation for Rectal Cancer in a Predominantly Hispanic Safety Net Hospital.

Background: Total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC) has shown promise in achieving pathologic complete response (pCR) and enabling organ preservation through watch-and-wait (WW) strategies. However, implementation of WW protocols in diverse patient populations and safety-net hospitals faces unique challenges. The objective of this study is to evaluate TNT outcomes and identify barriers to WW implementation in a predominantly Hispanic safety-net hospital in South Texas.

PELP1 Is a Novel Therapeutic Target in Hepatocellular Carcinoma.

Unlabelled: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the United States, with a median survival period of approximately 10 months. There is an urgent need for the development of effective targeted therapies for the treatment of HCC. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) signaling is implicated in the progression of many cancers, although its specific contribution to the progression of HCC is not yet well understood.

Adequate assessment yields appropriate care-the role of geriatric assessment and management in older adults with cancer: a position paper from the ESMO/SIOG Cancer in the Elderly Working Group.

With the aging population, older adults constitute a growing proportion of the new cancer cases. Given the heterogeneous health status among older adults and their susceptibility to aging-related vulnerabilities, understanding their diversity and its implications becomes increasingly crucial for prognostication and guiding diagnostics, treatment decisions, and follow-up, as well as informing supportive care interventions. Geriatric assessment and management (GAM) refers to the comprehensive evaluation of an older individual's health status with subsequent management plans focusing on both oncologic and non-oncologic interventions.

Comparing the Accuracy of Traditional vs. FHIR®-Based Extraction of Electronic Health Record Data for Two Clinical Trials.

While pilots and production use of software based on the Health Level Seven (HL7®) Fast Healthcare Interoperability Resources (FHIR®) standard are increasing in clinical research, we lack consistent evaluative data on important outcomes, such as data accuracy. We compared the accuracy of EHR collected, FHIR® extracted data (called EHR-to-eCRF data collection) to traditional clinical trial data collection. The accuracy rate for EHR-collected data was significantly higher than for the same data collected through traditional methods.

Lymph node metrics following neoadjuvant therapy to refine patient selection for adjuvant chemotherapy in resected pancreatic cancer: A multi-institutional analysis.

Background: In patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high-risk features on histopathologic examination. We evaluated the interaction between post-NAT lymph node metrics and AC receipt on survival.

Methods: Patients who received NAT followed by pancreatectomy (2010-2020) at seven centers were reviewed.

Oncogenic pathway signatures predict the risk of progression and recurrence in well-differentiated pancreatic neuroendocrine tumors.

Background: Pancreatic neuroendocrine tumors (pNETs) are genomically diverse tumors. The management of newly diagnosed well-differentiated pNETs is limited by a lack of sensitivity of existing biomarkers for prognostication. Our goal was to investigate the potential utility of genetic markers as a predictor of progression-free survival (PFS) and recurrence-free survival (RFS).

The RAD51 S181P mutation shortens lifespan of female mice.

RAD51 is critical to the homologous recombination (HR) pathway that repairs DNA double strand breaks (DSBs) and protects replication forks (RFs). Previously, we showed that the S181P (SP) mutation in RAD51 causes defective RF maintenance but is proficient for DSB repair. Here we report that SP/SP female mice exhibit a shortened lifespan compared to +/+ females but not males.

Sacituzumab Govitecan in patients with breast cancer brain metastases and recurrent glioblastoma: a phase 0 window-of-opportunity trial.

Sacituzumab Govitecan (SG) is an antibody-drug conjugate that has demonstrated efficacy in patients with TROP-2 expressing epithelial cancers. In a xenograft model of intracranial breast cancer, SG inhibited tumor growth and increased mouse survival. We conducted a prospective window-of-opportunity trial (NCT03995706) at the University of Texas Health Science Center at San Antonio to examine the intra-tumoral concentrations and intracranial activity of SG in patients undergoing craniotomy for breast cancer with brain metastases (BCBM) or recurrent glioblastoma (rGBM).