Emerging Therapeutic Agents for Colorectal Cancer

Nalli, Marianna; Puxeddu, Michela; Regina, Giuseppe La; Gianni, Stefano; Silvestri, Romano

doi:10.3390/molecules26247463

Cited by 16 publications

(27 citation statements)

References 182 publications

(187 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The effect of Imatinib treatment on CMS4 CRC was assessed in the clinical proof-of-concept study ImPACCT, in which patients with newly-diagnosed CMS4 CRC were treated with imatinib two weeks prior surgery [ 6 , 33 ]. By analysis of pre- and post-treatment samples, we recently demonstrated that imatinib mitigates the aggressive features of CMS4 CRC in this clinical study (Peters et al, submitted [ 34 ]), lending support for the concept of KIT-targeted treatment in the clinical management of CMS4 CRC [ 35 ].…”

Section: Discussionsupporting

confidence: 52%

KIT promotes tumor stroma formation and counteracts tumor-suppressive TGFβ signaling in colorectal cancer

et al. 2022

View full text Add to dashboard Cite

Expression profiling has identified four consensus molecular subtypes (CMS1-4) in colorectal cancer (CRC). The receptor tyrosine kinase KIT has been associated with the most aggressive subtype, CMS4. However, it is unclear whether, and how, KIT contributes to the aggressive features of CMS4 CRC. Here, we employed genome-editing technologies in patient-derived organoids (PDOs) to study KIT function in CRC in vitro and in vivo. CRISPR-Cas9-mediated deletion of the KIT gene caused a partial mesenchymal-to-epithelial phenotype switch and a strong reduction of intra-tumor stromal content. Vice versa, overexpression of KIT caused a partial epithelial-to-mesenchymal phenotype switch, a strong increase of intra-tumor stromal content, and high expression of TGFβ1. Surprisingly, the levels of phosphorylated SMAD2 were significantly lower in KIT-expressing versus KIT-deficient tumor cells. In vitro analyses showed that TGFβ signaling in PDOs limits their regenerative capacity. Overexpression of KIT prevented tumor-suppressive TGFβ signaling, while KIT deletion sensitized PDOs to TGFβ-mediated growth inhibition. Mechanistically, we found that KIT expression caused a strong reduction in the expression of SMAD2, a central mediator of canonical TGFβ signaling. We propose that KIT induces a pro-fibrotic tumor microenvironment by stimulating TGFβ expression, and protects the tumor cells from tumor-suppressive TGFβ signaling by inhibiting SMAD2 expression.

show abstract

Section: Discussionsupporting

confidence: 52%

KIT promotes tumor stroma formation and counteracts tumor-suppressive TGFβ signaling in colorectal cancer

et al. 2022

View full text Add to dashboard Cite

show abstract

“…The Ki-67 expression level was lower in the H/5-Fu-F/H-PA group than in the Rg3-H/F/H-PA group (*** p < .001) ( Figure 6D ). VEGF is a kind of protein crucial for tumor angiogenesis (Nalli et al., 2021 ). The VEGF expression level was the lowest in Rg3-H/5-Fu-F/H and Rg3-H/5-Fu-F/H-PA groups ( Figure 6A,E ).…”

Section: Resultsmentioning

confidence: 99%

The treatment efficacy of three-layered functional polymer materials as drug carrier for orthotopic colon cancer

et al. 2022

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a worldwide disease posing serious threats to people’s life. Surgery and postsurgical chemotherapy are still the first choices to control the rapid progression of cancer. However, tumor recurrence and even distant metastasis are prone to occur. As a result, it is in urgent demand to find a new method to control CRC progression while inhibiting distant metastasis. On this basis, this study developed the three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials. The Chinese traditional drugs 20 (S)-ginsenoside Rg3 (Rg3) and chemotherapeutic agent 5-fluorouracil (5-Fu) were loaded in the inner hydrogel and middle fibrous membrane and could be constantly released at the same time and space. The outer hydrogel was decorated with phenylboronic acid (PA) to interact with sialic acid expressed on the CRC cell surface. The composite materials possessed biocompatibility and showed no toxicity to normal human intestinal mucosa endothelial cells HIEC. According to the results, the cell viability of CT26 could be significantly decreased in vitro . The three-layered functionalized materials inhibited the original tumor progression and distant tumor metastasis to the liver in an orthotopic colon cancer mouse model by increasing the caspase3 expression and inhibiting the expressions of Bcl-2, Ki-67, and VEGF. In addition, the functions of major organs were not significantly damaged. Our study provides a safe and efficacious method of this three-layered functionalized hydrogel-fibrous membrane-hydrogel composite materials for CRC treatment.

show abstract

“…It is one of the important identified oncogenes whereby downregulating these pathways becomes a target for tyrosine kinase inhibitors (TKIs). 64 Targeting growth factor receptors is one of the important mechanisms for the emerging therapeutic agents against CRC. These growth factors include platelet-derived growth factor receptors (PDGFRs), fibroblast growth factor receptors (FGFRs), vascular endothelial growth factor receptors (VEGFRs) and others.…”

Section: Emerging Oral Therapeutic Agents For Treating Colorectal Can...mentioning

confidence: 99%

“… 65 Nintedanib is approved in Europe and the USA, with 150 mg twice daily as a standard adult dose. 64 …”

Section: Emerging Oral Therapeutic Agents For Treating Colorectal Can...mentioning

confidence: 99%

See 1 more Smart Citation

Current Advances in Chitosan Nanoparticles Based Oral Drug Delivery for Colorectal Cancer Treatment

Choukaife¹,

Seyam²,

Alallam³

et al. 2022

IJN

View full text Add to dashboard Cite

As per the WHO, colorectal cancer (CRC) caused around 935,173 deaths worldwide in 2020 in both sexes and at all ages. The available anticancer therapies including chemotherapy, radiotherapy and anticancer drugs are all associated with limited therapeutic efficacy, adverse effects and low chances. This has urged to emerge several novel therapeutic agents as potential therapies for CRC including synthetic and natural materials. Orally administrable and targeted drug delivery systems are attractive strategies for CRC therapy as they minimize the side effects, enhance the efficacy of anticancer drugs. Nevertheless, oral drug delivery till today faces several challenges like poor drug solubility, stability, and permeability. Various oral nano-based approaches and targeted drug delivery systems have been developed recently, as a result of the ability of nanoparticles to control the release of the encapsulant, drug targeting and reduce the number of dosages administered. The unique physicochemical properties of chitosan polymer assist to overcome oral drug delivery barriers and target the colon tumour cells. Chitosan-based nanocarriers offered additional improvements by enhancing the stability, targeting and bioavailability of several anti-colorectal cancer agents. Modified chitosan derivatives also facilitated CRC targeting through strengthening the protection of encapsulant against acidic and enzyme degradation of gastrointestinal track (GIT). This review aims to provide an overview of CRC pathology, therapy and the barriers against oral drug delivery. It also emphasizes the role of nanotechnology in oral drug targeted delivery system and the growing interest towards chitosan and its derivatives. The present review summarizes the relevant works to date that have studied the potential applications of chitosan-based nanocarrier towards CRC treatment.

show abstract

Emerging Therapeutic Agents for Colorectal Cancer

Cited by 16 publications

References 182 publications

KIT promotes tumor stroma formation and counteracts tumor-suppressive TGFβ signaling in colorectal cancer

KIT promotes tumor stroma formation and counteracts tumor-suppressive TGFβ signaling in colorectal cancer

The treatment efficacy of three-layered functional polymer materials as drug carrier for orthotopic colon cancer

Current Advances in Chitosan Nanoparticles Based Oral Drug Delivery for Colorectal Cancer Treatment

Contact Info

Product

Resources

About