The role of magnetic resonance imaging (MRI) in rectal cancer management has significantly increased over the last decade, in line with more personalized treatment approaches. Total neoadjuvant treatment (TNT) plays a pivotal role in the shift from traditional surgical approach to non-surgical approaches such as ‘watch-and-wait’. MRI plays a central role in this evolving landscape, providing essential morphological and functional data that support clinical decision-making. Key MRI-based biomarkers, including circumferential resection margin (CRM), extramural venous invasion (EMVI), tumour deposits, diffusion-weighted imaging (DWI), and MRI tumour regression grade (mrTRG), have proven valuable for staging, response assessment, and patient prognosis. Functional imaging techniques, such as dynamic contrast-enhanced MRI (DCE-MRI), alongside emerging biomarkers derived from radiomics and artificial intelligence (AI) have the potential to transform rectal cancer management offering data that enhance T and N staging, histopathological characterization, prediction of treatment response, recurrence detection, and identification of genomic features. This review outlines validated morphological and functional MRI-derived biomarkers with both prognostic and predictive significance, while also exploring the potential of radiomics and artificial intelligence in rectal cancer management. Furthermore, we discuss the role of rectal MRI in the ‘watch-and-wait’ approach, highlighting important practical aspects in selecting patients for non-surgical management.

Background and Objectives: Rectal cancer accounts for approximately one-third of colorectal cancers, with over 340,000 deaths globally in 2022. Despite advancements in treatment, the five-year overall survival for locally advanced rectal cancer (LARC) remains at 74%, with significant morbidity. B7H3 (CD276), an immune checkpoint protein, plays a role in tumor progression and resistance to therapy, and correlates with poor prognosis in various cancers, including colorectal cancer. This study aims to evaluate the expression of B7H3 in LARC and its impact on overall complete response (oCR) rates to neoadjuvant therapy. Methods: A retrospective study was conducted on 60 patients with LARC who received neoadjuvant chemoradiation (nCRT) followed by total mesorectal excision (TME). B7H3 expression was assessed using immunohistochemistry on surgical specimens. Expression levels were categorized as high or low based on a composite score, and their association with oCR rates was analyzed. Results: High B7H3 expression was observed in 60% of patients, with 73.5% showing expression in more than 50% of tumor cells. Patients who achieved oCR had significantly lower B7H3 expression compared to those with residual disease (p < 0.001). No nuclear expression of B7H3 was detected. No significant correlation was found between B7H3 expression and other clinicopathological variables, except for a higher likelihood of non-restorative surgery in patients with elevated B7H3 levels (p = 0.049). Mucinous adenocarcinoma had high expression of B7H3. Conclusions: Elevated B7H3 expression is associated with reduced oCR rates in LARC, highlighting its potential role as a prognostic biomarker. Further studies with larger cohorts are warranted to validate these findings and explore B7H3-targeted therapies as a treatment strategy for LARC.

Background/Objectives: Combining heterocyclic fragments provides a strategy for developing compounds for exploratory anticancer evaluation. This study aimed to synthesize and characterize five thiazolyl-methylthio-1,3,4-thiadiazolyl-quinazolin-4(3H)-one compounds (5a–e), assess their properties in silico, and investigate the selected ones for cytotoxicity and their effects on irradiation-associated DNA lesions. Methods: Structures were characterized by IR, HRMS, and ¹H- and ¹³C-NMR spectroscopy. Computational studies included physicochemical and ADMETox predictions, multi-platform target prediction, and molecular docking to A2A, Erβ, and CDK5. Compounds 5a and 5b were evaluated for cytotoxicity and cell-death profiles on one colorectal cancer (CRC) cell line (HT-29), two breast cancer (BC) cell lines (MCF-7 and MDA-MB-231), and one healthy fibroblast cell line (BJ), using cisplatin (Cis) as a reference. DNA lesions were assessed by the Comet assay in both breast cancer models before, immediately after, and 24 h after 4 Gy irradiation. Results: Compounds 5a–e were obtained in yields of 45.17–83.27%. Compounds 5a and 5b had lower 24-h IC₅₀ values than cisplatin in MCF-7 cells, but higher values in the other tested cell lines. Compound 5b showed higher selectivity indexes than both 5a and cisplatin across the cancer models, although its values of 1.14–1.34 indicated modest selectivity. Cell-death profiles differed between treatments, with larger necrotic fractions following 5a or 5b treatment in MCF-7 cells. Both compounds were associated with higher post-irradiation lesion scores than untreated irradiated controls. Scores increased further at 24 h in MCF-7 cells but decreased in MDA-MB-231 (triple-negative) cells. Pre-irradiation scores were also elevated in treated MCF-7 cells. Computational profiling identified comparatively more favorable predicted solubility for 5a and 5b. Cross-platform ADMET comparison consistently indicated low Caco-2 permeability, CYP3A4 inhibition, potential liver-injury risk, and high plasma–protein binding, while several absorption, transporter, and safety endpoints remained discordant. Target predictions showed weak cross-platform convergence. Docking provided the strongest, although moderate, structural support for A2A binding by 5a–d. Conclusions: The findings support further investigation of 5a and 5b, particularly their effects on irradiation-associated DNA lesions. Priorities include improving potency and selectivity, validating in silico predictions, and evaluating radiosensitizing potential through clonogenic survival studies.