AXL receptor as an emerging molecular target in colorectal cancer

De Rosa, Lucia; Di Stasi, Rossella; Fusco, Virginia; D'Andrea, Luca D.

doi:10.1016/j.drudis.2024.104005

Cited by 2 publications

(1 citation statement)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to its role in promoting cancer progression and therapy resistance, AXL has emerged as a potential therapeutic target in cancer treatment. Inhibitors targeting AXL signaling are being investigated in preclinical and clinical studies, either as single agents or in combination with other therapies, with the aim of inhibiting tumor growth and metastasis and overcoming therapy resistance [62][63][64][65].…”

Section: Discussionmentioning

confidence: 99%

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

Lima,

Machado-Neto

2024

Kinases and Phosphatases

View full text Add to dashboard Cite

Cancer, characterized by uncontrolled cell growth and metastasis, represents a significant challenge to public health. The IGF1/IGF1R axis plays a pivotal role in tumor proliferation and survival, presenting an attractive target for intervention. NT157, a small molecule tyrphostin, has emerged as a promising inhibitor of this axis, displaying potent antineoplastic effects across various cancer types. This review synthesizes the literature on NT157’s mechanism of action and its impact on cellular processes in experimental cancer models. Initially identified for inducing the serine phosphorylation of IRS1 and IRS2, leading to their degradation and inhibiting the IGF1R signaling cascade, subsequent studies revealed additional targets of NT157, including STAT3, STAT5, and AXL, suggesting a multifaceted mechanism. Experimental evidence demonstrates that NT157 effectively suppresses tumor growth, metastasis, and angiogenesis in diverse cancer models. Additionally, NT157 enhances chemotherapy efficacy in combination therapy. Moreover, NT157 impacts not only tumor cells but also the tumor microenvironment, modulating inflammation and immune responses by targeting cancer-associated fibroblasts, myeloid cells, and immune cells, creating a suppressive milieu hindering tumor progression and metastasis. In conclusion, NT157 exhibits remarkable versatility in targeting multiple oncogenic pathways and hallmarks of cancer, underscoring its potential as a promising therapeutic agent.

show abstract

Section: Discussionmentioning

confidence: 99%

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

Lima,

Machado-Neto

2024

Kinases and Phosphatases

View full text Add to dashboard Cite

show abstract

Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance

Tardito,

Matis,

Zocchi

et al. 2024

IJMS

View full text Add to dashboard Cite

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Therefore, the need for new therapeutic strategies is still a challenge. Surgery and chemotherapy represent the first-line interventions; nevertheless, the prognosis for metastatic CRC (mCRC) patients remains unacceptable. An important step towards targeted therapy came from the inhibition of the epidermal growth factor receptor (EGFR) pathway, by the anti-EGFR antibody, Cetuximab, or by specific tyrosine kinase inhibitors (TKI). Cetuximab, a mouse–human chimeric monoclonal antibody (mAb), binds to the extracellular domain of EGFR thus impairing EGFR-mediated signaling and reducing cell proliferation. TKI can affect the EGFR biochemical pathway at different steps along the signaling cascade. Apart from Cetuximab, other anti-EGFR mAbs have been developed, such as Panitumumab. Both antibodies have been approved for the treatment of KRAS-NRAS wild type mCRC, alone or in combination with chemotherapy. These antibodies display strong differences in activating the host immune system against CRC, due to their different immunoglobulin isotypes. Although anti-EGFR antibodies are efficient, drug resistance occurs with high frequency. Resistant tumor cell populations can either already be present before therapy or develop later by biochemical adaptations or new genomic mutations in the EGFR pathway. Numerous efforts have been made to improve the efficacy of the anti-EGFR mAbs or to find new agents that are able to block downstream EGFR signaling cascade molecules. Indeed, we examined the importance of analyzing the anti-EGFR antibody–drug conjugates (ADC) developed to overcome resistance and/or stimulate the tumor host’s immunity against CRC growth. Also, patient-derived CRC organoid cultures represent a useful and feasible in vitro model to study tumor behavior and therapy response. Organoids can reflect tumor genetic heterogeneity found in the tissue of origin, representing a unique tool for personalized medicine. Thus, CRC-derived organoid cultures are a smart model for studying the tumor microenvironment and for the preclinical assay of anti-EGFR drugs.

show abstract

AXL receptor as an emerging molecular target in colorectal cancer

Cited by 2 publications

References 76 publications

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

NT157 as an Anticancer Drug Candidate That Targets Kinase- and Phosphatase-Mediated Signaling

Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance

Contact Info

Product

Resources

About