Wide-field optical redox imaging with leading-edge detection for assessment of patient-derived cancer organoids.

Unlabelled: Patient-derived cancer organoids (PDCOs) are a valuable model to recapitulate human disease in culture with important implications for drug development. However, current methods for assessing PDCOs are limited. Label-free imaging methods are a promising tool to measure organoid level heterogeneity and rapidly screen drug response in PDCOs.

Phase I/II Trial of Perioperative Avelumab in Combination With Chemoradiation in the Treatment of Stage II/III Resectable Esophageal and Gastroesophageal Junction Cancer.

Background And Objectives: Standard treatment of patients with stage II/III esophageal or gastroesophageal junction (E/GEJ) cancer involves neoadjuvant chemoradiation (nCRT), resection, and immunotherapy. Our trial evaluated the addition of perioperative avelumab to standard treatments.

Methods: Patients with resectable E/GEJ cancers received avelumab with nCRT and adjuvant avelumab after resection.

Development of KRAS Inhibitors and Their Role for Metastatic Colorectal Cancer.

Colorectal cancer (CRC) is a heterogeneous group of diseases comprising several molecular subtypes. Comprehensive DNA sequencing is now standard practice to identify these subtype. Until recently, KRAS mutation status in metastatic CRC was primarily used as a biomarker to predict resistance to EGFR inhibition.

The dichotomous roles of microbial-modified bile acids 7-oxo-DCA and isoDCA in intestinal tumorigenesis.

The gut microbiota has a significant impact on the development and function of intestinal epithelial cells (IECs) by modifying bile acid (BA) metabolites. Recently, specific gut microbiome-derived BAs, such as 7-oxo-deoxycholic acid (7-oxo-DCA) and isodeoxycholic acid (isoDCA), have been identified to be shifted inversely in colitis and hepatic liver diseases. Although the responsible gut microbes have been identified, metabolites' effects on IECs remain largely unclear.

Cellpose as a reliable method for single-cell segmentation of autofluorescence microscopy images.

Autofluorescence microscopy uses intrinsic sources of molecular contrast to provide cellular-level information without extrinsic labels. However, traditional cell segmentation tools are often optimized for high signal-to-noise ratio (SNR) images, such as fluorescently labeled cells, and unsurprisingly perform poorly on low SNR autofluorescence images. Therefore, new cell segmentation tools are needed for autofluorescence microscopy.

State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation.

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC.

Modified FOLFOX6 plus bevacizumab with and without nivolumab for first-line treatment of metastatic colorectal cancer: phase 2 results from the CheckMate 9X8 randomized clinical trial.

Background: Standard first-line therapies for metastatic colorectal cancer (mCRC) include fluoropyrimidine-containing regimens with oxaliplatin and/or irinotecan and a biologic agent. Immunotherapy may enhance antitumor activity in combination with standard therapies in patients with mCRC. Here, we present phase 2 results of nivolumab plus standard-of-care therapy (SOC; 5-fluorouracil/leucovorin/oxaliplatin/bevacizumab) versus SOC in the first-line treatment of patients with mCRC (CheckMate 9X8).

Minimal Residual Disease-Directed Adjuvant Therapy for Patients With Early-Stage Colon Cancer: CIRCULATE-US.

Background: The ability to detect circulating tumor DNA (ctDNA), a novel surrogate for minimal residual disease (MRD) for patients with solid tumors, has significantly evolved over the past decade. Several studies have shown that ctDNA may provide clinical insight into the biological dynamics of MRD. The CIRCULATE-US (NRG-GI008; NCT05174169) trial will aim to address the role of ctDNA for risk stratification to intensify and deintensify adjuvant chemotherapy for patients with early-stage colon cancer.

Treatment of Metastatic Colorectal Cancer: ASCO Guideline.

Purpose: To develop recommendations for treatment of patients with metastatic colorectal cancer (mCRC).

Methods: ASCO convened an Expert Panel to conduct a systematic review of relevant studies and develop recommendations for clinical practice.

Results: Five systematic reviews and 10 randomized controlled trials met the systematic review inclusion criteria.

Stromal remodeling regulates dendritic cell abundance and activity in the tumor microenvironment.

Stimulatory type 1 conventional dendritic cells (cDC1s) engage in productive interactions with CD8 effectors along tumor-stroma boundaries. The paradoxical accumulation of "poised" cDC1s within stromal sheets is unlikely to simply reflect passive exclusion from tumor cores. Drawing parallels with embryonic morphogenesis, we hypothesized that invasive margin stromal remodeling generates developmentally conserved cell fate cues that regulate cDC1 behavior.

Inhibition of B-cell lymphoma 2 family proteins alters optical redox ratio, mitochondrial polarization, and cell energetics independent of cell state.

Significance: The optical redox ratio (ORR) [autofluorescence intensity of the reduced form of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)/flavin adenine dinucleotide (FAD)] provides a label-free method to quantify cellular metabolism. However, it is unclear whether changes in the ORR with B-cell lymphoma 2 (Bcl-2) family protein inhibition are due to metabolic stress alone or compromised cell viability.

Aim: Determine whether ABT-263 (navitoclax, Bcl-2 family inhibitor) changes the ORR due to changes in mitochondrial function that are independent of changes in cell viability.

Clinical utility of a regional precision medicine molecular tumor board and challenges to implementation.

Purpose: Molecular tumor boards provide precision treatment recommendations based on cancer genomic profile. However, practical barriers limit their benefits. We studied the clinical utility of the precision medicine molecular tumor board (PMMTB) and described challenges with PMMTB implementation.

Impact of baseline culture conditions of cancer organoids when determining therapeutic response and tumor heterogeneity.

Representative models are needed to screen new therapies for patients with cancer. Cancer organoids are a leap forward as a culture model that faithfully represents the disease. Mouse-derived cancer organoids (MDCOs) are becoming increasingly popular, however there has yet to be a standardized method to assess therapeutic response and identify subpopulation heterogeneity.

Technologies to Assess Drug Response and Heterogeneity in Patient-Derived Cancer Organoids.

Patient-derived cancer organoids (PDCOs) are organotypic 3D cultures grown from patient tumor samples. PDCOs provide an exciting opportunity to study drug response and heterogeneity within and between patients. This research can guide new drug development and inform clinical treatment planning.

Phase II Study of Copanlisib in Patients With Tumors With Mutations: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1F.

Purpose: Activating mutations in are observed across multiple tumor types. The NCI-MATCH (EAY131) is a tumor-agnostic platform trial that enrolls patients to targeted therapies on the basis of matching genomic alterations. Arm Z1F evaluated copanlisib, an α and δ isoform-specific phosphoinositide 3-kinase (PI3K) inhibitor, in patients with mutations (with or without loss).