Colon Cancer

Thereby, MDM4 enhances the stability of GPX4 protein, inhibiting ferroptosis, increasing the resistance of colon cancer patients to chemotherapy, and promoting colon cancer progression. These findings elucidate the ferroptosis inhibition effect of MDM4 via regulating TRIM21/GPX4 on p53-mutated colon cancer and provide a potential therapeutic strategy for colon cancer therapy.

Currently, no SHP2 inhibitors have been approved for clinical use, and colorectal cancer (CRC) cells exhibited frequent resistance to reported SHP2 inhibitors, such as SHP099 and TNO155. A8 significantly suppressed in vivo tumor growth in a CT26 mouse model and activated immunomodulatory effects in tumor microenvironment. Our work demonstrated that A8 has the potential to be a lead compound for the further development of SHP2 inhibitor and the treatment of CRC.

These rhenium(I) tricarbonyl complexes also slightly increased ROS production and significantly decreased the mitochondrial membrane potential by 50 % (5eRe) and 45 % (6dRe) compared to untreated cells and cells treated with 5e and 6d. These results suggest that the cytotoxic effects of these compounds are mediated by their effects on mitochondrial membrane potential and the subsequent increase in ROS production.

The deletion of SPOP, which led to increased stability of the RIPK3 protein, intensified LPS/sMAC/zVAD-induced necroptotic cell death in colon cancer cells. These findings underscore the critical role of the SPOP-mediated RIPK3 stability regulation pathway in controlling necroptotic cell death.

Dual-luciferase reporter assays confirmed the binding relationship between lncXIST and miR-17-5p, as well as miR-17-5p and PDGFRA. Collectively, our results highlight the novel role of lncXIST in facilitating macrophage polarization by sponging miR-17-5p and regulating PDGFRA expression.

© 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

LncRNA AF117829.1 is closely related to the prognosis, immunological characteristics and immunotherapy response of CRC patients and promotes malignant progression of CRC by targeting OR7C1. Moreover, AF117829.1 may be a potential therapeutic target for CRC patients.

TCM displayed a potential enhanced anti-tumor efficacy of PD-1/PD-L1 inhibitors on six types of tumor including colon, breast, colorectal, melanoma, and bladder cancer in animals. However, due to significant heterogeneity in the included studies, caution should be exercised regarding the results. More high-quality randomized controlled animal experiments are need.

Lastly, DDR1 was found positively correlated with collagen I expression in MSS CRC specimens. These findings indicated that targeting DDR1 or its inhibitor 7rh might be potential strategy for overcoming immunotherapy resistance in MSS CRC.

The association for colon cancer was positive in individuals with high waist circumference (hazard ratio &lsqb;95% CI], 1.69 &lsqb;1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio &lsqb;95% CI], 0.86 &lsqb;0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.

Clinically used drugs deferiprone and minocycline reduced mitochondrial iron and superoxide levels, resulting in decreased colon tumor cell growth in vitro and in vivo. Manipulating the mitochondrial iron uptake protein MCU (mitochondrial calcium uniporter) also affected cell and xenograft tumor growth. This study suggests that therapies aimed at reducing mitochondrial iron levels may effectively inhibit colon tumor growth, particularly in patients with low PINK1 expression.

Accordingly, the biologically derived nanovesicles from ginger (GDNVs) with excellent P. gingivalis elimination ability are explored to transport the clinically used drug paclitaxel (PTX) for potentiating the therapeutic efficiency...By evaluating both P. gingivalis-infected tumor cells and P. gingivalis-infiltrated tumor-bearing mice, P-GDNVs show a much enhanced tumor cell killing effect, as compared with free PTX. This naturally occurring nanotherapeutic system represents an effective bioactive material for targeted elimination of host microbiota to boost therapeutic response, showing great promise to combat commensal microbiota-rich tumors.

At the same time, the adjacent normal mucosa was negative for cyclin D2 staining. The results suggest that the increased cyclin D2 expression by L1 is required to induce proliferative, motile tumor development in CRC tissue and can serve as a diagnostic marker and a target for CRC therapy.

Finally, the steps for flow cytometry-based evaluation of tumor cell apoptosis by assessment of Caspase 3/7 staining are detailed. The implementation of this standardized protocol using patient-derived specimens offers a superior alternative to immortalized cell lines for assessing therapeutic efficacy, increasing the probability of translation of preclinical research findings, and bolstering the development of innovative therapeutic strategies for CRC.

In conclusion, miR-106b-5p expression was significantly upregulated in colon cancer tissues, with higher expression levels demonstrated in LCC compared with RCC. High miR-106b-5p expression in RCC was identified as an independent prognostic factor, whilst its expression in LCC did not show a significant association with prognosis.

However, the prognosis of patients in the low-risk group with high CEA levels improved with a 6-month adjuvant treatment with oxaliplatin to a similar level to that of all patients with low CEA levels in the low-risk group. In conclusion, the present study suggested that the duration of adjuvant chemotherapy with oxaliplatin should not be shortened in patients with high preoperative CEA levels, even in the low-risk group.

In addition, our research suggests that VEGFB not only promotes angiogenesis but is also involved in the tumor microenvironment and immune regulation. The SHNG17-miR-375-VEGFB regulatory axis provides a potential therapeutic target for COAD, highlighting VEGFB's role in immune activation during anti-angiogenic therapy and potential reversal of drug resistance.

Targeting Wnt signaling through the modulation of macropinocytosis and broader membrane trafficking pathways presents a promising therapeutic strategy, with several candidates already in early clinical trials. These emerging approaches underscore the potential of targeting Wnt and its associated membrane trafficking processes for CRC treatment, aligning with the development of innovative therapies.

The authors described the molecular characteristics of CRC. Loss of LRP1B leads to changes in immune cell infiltration and can be used as a therapeutic target for colorectal cancer.

Uptake occurred in a dose-dependent manner for PLA-NCs sized at 260 ± 51 nm, with only 30 % internalization at 2 mg/mL concentration after 24 to 48 h. Notably, smaller PLA-NCs with a mean size of 170 ± 64 nm achieved nearly 100 % uptake across all tested cell types after 48 h, indicating that particle size significantly influenced cellular uptake.

Interestingly, greater OGA expression resulted in both lower overall survival of colon carcinoma patients and lower disease-free survival of rectum carcinoma patients. Therefore, our data indicates that OGA expression correlates with CSC markers and directly impacts the survival of colorectal carcinoma patients.

RES down-regulates the pyroptosis of HT29 cells induced by LPS/ATP and the expression of pyroptosis-related indicators NLRP3, ASC, CASP1, IL-18, IL-1β and inflammatory factors TNF-α and IL-6 in the inflammatory response and inhibits the occurrence of pyroptosis. The mechanism is related to the inhibition of NF-κB pathway activity.

In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers.

P2, N=83, Active, not recruiting, Vejle Hospital | Recruiting --> Active, not recruiting | Trial completion date: Oct 2024 --> Mar 2025 | Trial primary completion date: Oct 2024 --> Mar 2025

P1, N=122, Terminated, Novartis Pharmaceuticals | Trial completion date: Jan 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jan 2025 --> Sep 2024; The decision of early termination was made due to business reasons, and was not based on any safety concerns for any of the treatment combinations.

P=N/A, N=1839, Recruiting, San Luigi Gonzaga Hospital

Both assays showed comparable sensitivity in establishing MSI status for CRC and the expanded spectrum of non-CRC tumors. Advantages such as increased number of LMR loci in the Promega assay and the need for only tumor specimen in the Idylla assay increase the utility of these assays in determination of MSI status in a variety of cancers.

Given the importance of timely, comprehensive molecular test results to inform appropriate treatment decisions in NSCLC and CRC, these results suggest that the rapid in-house GeneXus NGS system can reduce TAT with comparable failure rates and alteration detection rates compared to other testing methods. Further studies evaluating the impact of the rapid OPA compared to other methods on patient care, as well as the economics of different molecular tests, are ongoing.

Growth and proliferation pathways are altered more in certain cancers than in others; however, the CC pathway is altered to a lesser extent but across cancers. The HRR pathway is predominantly altered in ovarian and prostate cancers. RTK/Ras and PI3K pathways have been well studied with smaller panels and established genes; however, large panels allow for inclusion of additional components of these pathways, and assessment of HRR and CC pathways more effectively.

P3, N=288, Not yet recruiting, Qilu Pharmaceutical Co., Ltd.

P1/2, N=240, Not yet recruiting, A2 Biotherapeutics Inc.

P1/2, N=856, Active, not recruiting, Loxo Oncology, Inc. | Recruiting --> Active, not recruiting

P=N/A, N=3787, Completed, Asan Medical Center

P3, N=700, Recruiting, IFOM ETS - The AIRC Institute of Molecular Oncology | Not yet recruiting --> Recruiting

P2, N=62, Suspended, Oslo University Hospital | Recruiting --> Suspended | Trial primary completion date: Mar 2024 --> Dec 2024

Altogether, these results demonstrated that TiY has a strong potential for visualizing CRC by fluorescence imaging in various preclinical models, which can be further translated for clinical use such as fluorescence-guided surgery. Furthermore, our data indicate that TiY is preferentially uptaken by cells with EMT induction and progression, and overexpressing vimentin and Zeb1 in patients with CRC.

P=N/A, N=110, Not yet recruiting, The Second Hospital & Clinical Medical School,Lanzhou University; The Second Hospital & Clinical Medical School,Lanzhou University

P=N/A, N=60, Not yet recruiting, Qilu Hospital of Shandong University; Qilu Hospital of Shandong University

P=N/A, N=8000, Not yet recruiting, First Affiliated Hospital of Kunming Medical University; First Affiliated Hospital of Kunming Medical University

P2, N=37, Not yet recruiting, Shanghai East Hospital; Shanghai East Hospital

The expressions of MSH2, MSH6, and villin are closely correlated with the pathological features of colon cancer patients. Evaluating the expression of the three proteins may assist in the clinical diagnosis, treatment, and prognosis evaluation of colon cancer.

INPP4B is highly expressed in CRC tissues and significantly correlated with lymph node metastasis, neural invasion, and patient prognosis. MMP7 may mediate the role of INPP4B in promoting CRC cell migration and invasion.