Small-molecule drugs of colorectal cancer: Current status and future directions

Yang, Yiren; Liu, Pengyu; Zhou, Mingyang; Yin, Linzhou; Wang, Miao; Liu, Ting; Jiang, Xiaowen; Gao, Huiyuan

doi:10.1016/j.bbadis.2023.166880

Cited by 5 publications

(2 citation statements)

References 185 publications

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“…With an ever-increasing understanding of genomic alterations among mCRC patients, there is a promising perspective in exploring novel approaches from recent advancements in genetics and immunology such as the development of therapies focused on changing the immunological phenotype of mCRC e.g., radioimmunotherapy ( 195 ) or photoimmunotherapy ( 196 ) holds promise for a broader application of immunotherapy in treating mCRC. Additionally, the potential benefits extend to adoptive cell therapy, small-molecule drug treatments ( 197 ), and leveraging recent advancements in nanotechnology ( 198 ). Progress in comprehending the role of microbiota in mCRC ( 199 , 200 ) may contribute to further improvements in overall survival rates.…”

Section: Discussionmentioning

confidence: 99%

Navigating through novelties concerning mCRC treatment—the role of immunotherapy, chemotherapy, and targeted therapy in mCRC

Zheng,

Włodarczyk,

Węgiel

et al. 2024

Front. Surg.

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Over the course of nearly six decades since the inception of initial trials involving 5-FU in the treatment of mCRC (metastatic colorectal cancer), our progressive comprehension of the pathophysiology, genetics, and surgical techniques related to mCRC has paved the way for the introduction of novel therapeutic modalities. These advancements not only have augmented the overall survival but have also positively impacted the quality of life (QoL) for affected individuals. Despite the remarkable progress made in the last two decades in the development of chemotherapy, immunotherapy, and target therapies, mCRC remains an incurable disease, with a 5-year survival rate of 14%. In this comprehensive review, our primary goal is to present an overview of mCRC treatment methods following the latest guidelines provided by the National Comprehensive Cancer Network (NCCN), the American Society of Clinical Oncology (ASCO), and the American Society of Colon and Rectal Surgeons (ASCRS). Emphasis has been placed on outlining treatment approaches encompassing chemotherapy, immunotherapy, targeted therapy, and surgery's role in managing mCRC. Furthermore, our review delves into prospective avenues for developing new therapies, offering a glimpse into the future of alternative pathways that hold potential for advancing the field.

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Section: Discussionmentioning

confidence: 99%

Navigating through novelties concerning mCRC treatment—the role of immunotherapy, chemotherapy, and targeted therapy in mCRC

Zheng,

Włodarczyk,

Węgiel

et al. 2024

Front. Surg.

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“…Nowadays, chemotherapy is still the primary treatment approach following surgical resection of colorectal cancer [ 4 ]. Irinotecan (IRT), an FDA-approved topoisomerase I inhibitor derived from the Chinese tree Camptotheca acuminate , is a first-line chemotherapeutic drug for metastatic colon or rectal carcinoma [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

Combination of miR159 Mimics and Irinotecan Utilizing Lipid Nanoparticles for Enhanced Treatment of Colorectal Cancer

Yang,

Liu,

Yang

et al. 2024

Pharmaceutics

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Colorectal cancer (CRC) ranks as the third most prevalent global malignancy, marked by significant metastasis and post-surgical recurrence, posing formidable challenges to treatment efficacy. The integration of oligonucleotides with chemotherapeutic drugs emerges as a promising strategy for synergistic CRC therapy. The nanoformulation, lipid nanoparticle (LNP), presents the capability to achieve co-delivery of oligonucleotides and chemotherapeutic drugs for cancer therapy. In this study, we constructed lipid nanoparticles, termed as LNP-I-V by microfluidics to co-deliver oligonucleotides miR159 mimics (VDX05001SI) and irinotecan (IRT), demonstrating effective treatment of CRC both in vitro and in vivo. The LNP-I-V exhibited a particle size of 118.67 ± 1.27 nm, ensuring excellent stability and targeting delivery to tumor tissues, where it was internalized and escaped from the endosome with a pH-sensitive profile. Ultimately, LNP-I-V significantly inhibited CRC growth, extended the survival of tumor-bearing mice, and displayed favorable safety profiles. Thus, LNP-I-V held promise as an innovative platform to combine gene therapy and chemotherapy for improving CRC treatment.

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Epigenetic modulation of autophagy pathway by small molecules in colorectal cancer: a systematic review

Zamani,

Safari,

Siri

et al. 2024

J Cancer Res Clin Oncol

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Purpose Colorectal cancer (CRC) remains a global health challenge with limited treatment success due to drug resistance. Recent research highlights the potential of small molecules to modulate CRC by targeting epigenetics or autophagy pathways. This systematic review explores the epigenetic effect of small molecules on autophagy in CRC, aiming to identify novel therapeutic strategies. Methods Following PRISMA guidelines, we systematically reviewed 508 studies from PubMed, Scopus, and Web of Science databases until August 13, 2023. Results Eight studies met inclusion criteria, examining the role of small molecules as epigenetic modulators (Histone acetylation/deacetylation, DNA methylation/demethylation and gene expression regulation by miRNAs) influencing the autophagy pathway in CRC. The studies encompassed in vitro and animal model in vivo studies. Small molecules exhibited diverse effects on autophagy in CRC. For instance, panobinostat promoted autophagy leading to CRC cell death, while aspirin inhibited autophagy flux, reducing aspirin-mediated CRC cell death. The epigenetic modulation of autophagy by various small molecules differently affects their anticancer effect, which underscores the complexity of therapeutic interventions. Conclusion Understanding the intricate dynamics among small molecules, epigenetic modifications, and autophagy in CRC is crucial for developing targeted therapeutic strategies. Considering the dual role of autophagy in tumorigenesis and tumor suppression, administration of these small molecules may differently affect the cancer cell fate and drug response or resistance based on their effect on the autophagy pathway. Therefore, recognition of the epigenetics mechanism of anticancer small molecules on autophagy may contribute to deciding how to prescribe them for better CRC treatment.

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Small-molecule drugs of colorectal cancer: Current status and future directions

Cited by 5 publications

References 185 publications

Navigating through novelties concerning mCRC treatment—the role of immunotherapy, chemotherapy, and targeted therapy in mCRC

Navigating through novelties concerning mCRC treatment—the role of immunotherapy, chemotherapy, and targeted therapy in mCRC

Combination of miR159 Mimics and Irinotecan Utilizing Lipid Nanoparticles for Enhanced Treatment of Colorectal Cancer

Epigenetic modulation of autophagy pathway by small molecules in colorectal cancer: a systematic review

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