Colorectal Cancer

Molecular docking identified potential protein targets, related to the CEO anticancer activity, in the form of PI3Kα, where the highest active theoretical inhibitor was calamenene (-7.5 kcal/mol). Docking results also showed that calamenene was the overall most active theoretical inhibitor for all docked proteins and indicated a potential presence of synergistic effects among all CEO constituents.

The comprehensive list of CEA-positive human tumor types demonstrates that CEA is expressed in a broad range of epithelial neoplasms, many of which might benefit from CEA serum monitoring and anti-CEA therapies.

The greatest expression of hepcidin is found in patients with metastatic CRC, and CRC patients with high hepcidin content have a worse survival rate than those with low hepcidin content. In the present article, we review the data supporting the prominent role of hepcidin in colon tumorigenesis and discuss how hepcidin inhibitors can help treat CRC patients in the metastatic setting with particular regard to the impact of hepcidin modulation on immunotherapeutic outcomes.

Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.

Furthermore, reduced MSI signal was observed in tumours with isolated MSH6 loss (p = 0.009 Ohio, p = 6.2 × 10-5 Manchester) and in both ECs and CRCs with germline defects, although this only reached significance in CRCs (p = 0.002). These results provide further evidence that ECs with MSH6 loss in particular and LS tumours in general have an attenuated MSI signal, providing support for current guidelines specifically recommending IHC for LS detection and immune checkpoint therapy assessment in EC.

We also observed a remarkable and specific accumulation of one Cer species, C20:4 Cer, generated predominantly by ceramide synthase 4, as a key factor required for 5-epi-induced ICD. Together, these data indicate that engagement of CB2, by 5-epi, alters regulation of the de novo ceramide synthesis pathway to generate Cer species that mediate ICD.

Synthesizing evidence from diverse studies, this review provides insights into the prognostic and predictive landscape of CRC, highlighting the potential clinical implications of identified determinants. Understanding the multifaceted nature of prognostic and predictive factors in CRC is imperative for the advancement of personalized treatment strategies and improvement of patient outcomes.

The management of metastatic colorectal cancer in patients harboring RAS mutations primarily involves chemotherapy, often combined with bevacizumab, as a standard first-line treatment...Further research is needed to validate these mechanisms and understand the impact of the neo-RAS wt phenomenon on long-term outcomes, such as overall survival and progression-free survival. This review provides a comprehensive overview of the current understanding of the neo-RAS wt phenomenon, including its incidence, potential mechanisms, and clinical implications.

In toto, these findings underscore how the WNT and TGF-Beta pathways may act differently in different ethnic groups with early-onset CRC. These findings may set a stage for developing new therapies tailored for reducing cancer health disparities.

Our findings demonstrate that WTAP-mediated m6A modification facilitated the progression of CRC through the YTHDF2-SOX1 axis and could serve as a potential therapeutic targeting for CRC.

In conclusion, Foxp3 + Treg-derived IL-10 was found to act on Foxp3 + Tregs and myeloid cells, thereby promoting lung metastasis formation. These findings provide insights into lung metastasis-related immunity and establish the groundwork for optimizing metastasis-targeting immunotherapies through targeting of IL-10 as a novel therapeutic strategy.

When combined with a vascular disrupting agent, A15-LY-NPs demonstrated three times greater drug accumulation in the tumor at 24 h compared to the control and showed a 93.7% tumor suppression rate in 4T1 tumors initiated at ∼500 mm3, significantly attenuating metastatic spread to the lungs and liver. This study presents an innovative approach for the precise and efficient delivery of TGF-β inhibitors to tumors, offering the potential to augment the efficacy of cancer therapeutics.

Functional characterization of the variant demonstrated that it could act as an allele-specific enhancer to distally facilitate the expression of CCND2 mediated by the transcription factor TEAD4. Overall, our study underscores the essential role of CCND2 in CRC development and delineates its regulatory mechanism mediated by rs4477507, establishing an epidemiological and biological link between genetic variation and CRC pathogenesis.

In conclusion, these findings uncover an unconventional role for DRD4 beyond its classic function as a neurotransmitter receptor. The intracellular signaling of DRD4 interacting with TGFBR1 can be targeted pharmacologically for CRC therapy.

Mitophagy-deficient tumors lack this anti-ferroptotic mechanism, unleashing the generation of lipid peroxidation and potent ferroptotic cell death induced by erastin, RSL3, cysteine deprivation, radiotherapy, and immunotherapy. In summary, patient-derived organoids of colorectal cancer patients for screening ferroptosis-sensitive tumors are established, providing a paradigm for identifying that patient-derived tumors are sensitive to ferroptosis-inducing therapies. This study concludes that mitophagy-deficient tumors are vulnerable to ferroptosis induction, which may lead to the development of new therapeutic strategies for tumors deficient in mitophagy.

The fact that WTAP protein expression levels lower while WTAP RNA expression remains high, lets us hypothesize a sort of inhibition of protein expression, but further studies are needed to clarify the mechanism. Although the results suggest a relationship between biological meaning and prognostic utility of WTAP, this prognostic utility must be confirmed by further studies on a larger sample.

The incidence of autophagy and the expressions of Beclin 1 and ATP binding cassette transporter G2 are different in left and right colon cancer, and autophagy may be involved in the occurrence of chemotherapy resistance. In this article, the roles of CDK9, ATP binding cassette transporter G2 and Beclin 1 in CRC were elucidated, emphasizing the linkages among them and providing potential therapeutic targets of CRC.

Primary colonic SRCC is a rare malignant tumor with atypical clinical symptoms, and timely identification and intervention are crucial for improving the prognosis.

SHARPIN was identified as an upregulated anti-apoptotic protein in CRC, and matrine exhibited anticancer effects by downregulating its expression. Thus, matrine appears to be a promising drug for CRC.

This review highlights the occurrence, characteristics, immobilisation, and potential applications of FOS-generating fungal FTases. Production, heterologous expression, molecular characteristics, and modelling of fungal FTases underpinning their biotechnological prospects are also discussed.

These findings underscore the critical role of CD19 within the tumor microenvironment, suggesting its potential as a biomarker and a therapeutic target in specific types of cancer.

Changtong Paste therapy can effectively regulate hemorheology, improve gastrointestinal hormone levels, promote gastrointestinal and immune function recovery, alleviate cancer-related fatigue, enhance quality of life, and shorten hospital stays after colorectal cancer surgery.

ADCY5 localized to stromal regions in both the ST and protein immunohistochemistry. Interestingly, both these significant genes are expressed in tissues other than the tumor itself, highlighting the complex interplay between the tumor and microenvironment, and that druggable targets may be found in the ability to modify how "normal" tissue interacts with tumors.

In conclusion, the mutation and expression characteristics of PRGs in CRC were comprehensively analyzed and a prognostic PRG signature was constructed in the present study. This signature may predict immune cell infiltration and therapeutic response in CRC, providing new insights into the prognosis and treatment of CRC.

The best serum protein signature model (IL7, CXCL12, IL10, IL15, CXCL1, and MCP-3) was able to distinguish CRC patients from healthy controls. These proteins were also involved in the occurrence and development of CRC.

Together, these data support FRS positively correlates with poor prognosis and therapy resistance. The PHA-793887 could be a potential FRS inhibitor to improving the effectiveness of CRC management via bolstering antitumor immunity.

The combination of IDO1 and HDAC inhibitors represents a promising strategy for CRC treatment, and NP-I/P is a candidate for clinical trials.

Elevated baseline lactate dehydrogenase was linked to shorter PFS. SHR-1701 combined with XELOX and bevacizumab demonstrated a manageable safety profile and potent antitumor activity in unresectable mCRC.

OX1 receptor activation induced orexin/β-arrestin-dependent internalisation, which was independent of the apoptotic pathway induced by orexins and antagonists. In addition, antagonists activate the Gq protein, suggesting its putative partial dissociation. These results suggest that the development of OX1 receptor targeting molecules, including orexin antagonists with antitumor properties, may pave the way for innovative cancer therapies.

Combining HSP70 and HSF1 inhibitors may be a promising anti-cancer strategy, offering a potential solution to overcome the negative feedback mechanism and enhance anti-cancer effects.

Additionally, during malignant progression of CRC, the transformation of CD8+ T cell cytotoxic and exhausted properties and macrophage pro-inflammatory and anti-inflammatory properties epitomized the cellular reprogramming phenomenon that the function of TME shifted from promoting immunity to suppressive immunity. Our study shed lights on refining personalized therapeutic regimens during malignant progression in left- and right-sided CRCs.

The vaccine candidate also demonstrated significant protective effect in mice upon challenging with Salmonella typhimurium. To the best of our knowledge, this is the first study reporting the expression of OmpC antigen in plants for potential use as vaccine against salmonellosis.

P1, N=7, Terminated, Mirati Therapeutics Inc. | Completed --> Terminated; The decision was made to terminate this study to further enrollment, as of 08 March 2022. The decision was made primarily due to a change in development strategy.

Our findings support the growing recognition of mosaicism as a critical factor in CRC susceptibility and underscore the importance of incorporating mosaicism screening into routine genetic testing for at-risk patients.

P=N/A, N=40, Recruiting, University of Alberta | N=30 --> 40 | Trial primary completion date: Dec 2024 --> Dec 2025

P=N/A, N=235, Completed, Shanghai Tong Ren Hospital | Recruiting --> Completed

P2, N=80, Active, not recruiting, AIO-Studien-gGmbH | Recruiting --> Active, not recruiting | Trial completion date: Nov 2026 --> Apr 2027 | Trial primary completion date: Nov 2026 --> Apr 2027

P1/2, N=386, Active, not recruiting, Mirati Therapeutics Inc. | Recruiting --> Active, not recruiting

P1/2, N=97, Active, not recruiting, NextCure, Inc. | Recruiting --> Active, not recruiting | N=209 --> 97

P=N/A, N=175, Recruiting, Cedars-Sinai Medical Center | N=300 --> 175

P2, N=166, Terminated, SOTIO Biotech AG | Active, not recruiting --> Terminated; Due to lack of expected efficacy shown at the time of the interim analysis

P2, N=40, Recruiting, ImmunityBio, Inc. | Active, not recruiting --> Recruiting | N=147 --> 40