Novel strategies to reverse chemoresistance in colorectal cancer

Abstract

Colorectal cancer (CRC) is a common gastrointestinal malignancy with high morbidity and fatality. Chemotherapy, as traditional therapy for CRC, has exerted well antitumor effect and greatly improved the survival of CRC patients.Nevertheless, chemoresistance is one of the major problems during chemotherapy for CRC and significantly limits the efficacy of the treatment and influences the prognosis of patients. To overcome chemoresistance in CRC, many strategies are being investigated. Here, we review the common and novel measures to combat the resistance, including drug repurposing (nonsteroidal anti-inflammatory drugs, metformin, dichloroacetate, enalapril, ivermectin, bazedoxifene, melatonin, and S-adenosylmethionine), gene therapy (ribozymes, RNAi, CRISPR/ Cas9, epigenetic therapy, antisense oligonucleotides, and noncoding RNAs), protein inhibitor (EFGR inhibitor, S1PR2 inhibitor, and DNA methyltransferase inhibitor), natural herbal compounds (polyphenols, terpenoids, quinones, alkaloids, and sterols), new drug delivery system (nanocarriers, liposomes, exosomes, and hydrogels), and combination therapy. These common or novel strategies for the reversal of chemoresistance promise to improve the treatment of CRC.

Exosome inhibition improves response to first‐line therapy in small cell lung cancer

“…In exosomes, encapsulating various biomolecules, including lipids, proteins, coding and non‐coding RNAs, and DNA species, promotes the survival and dissemination of cancer cells against stress, chemoresistance and immune surveillance 7–10 . Tumour‐derived exosomes have a critical role in the tumour environment through short‐ and long‐distance delivery of biological molecules 10–13 . Increasing evidence has shown that exosomes derived from tumour cells affect the proliferation and metastasis of recipient tumour cells 14–16 .…”

LAMP2A regulates cisplatin resistance in colorectal cancer through mediating autophagy

“…The survival rate (within 5 years) of CRC is still only about 50%. this low survival rate of CRC is highly related to its chemotherapy resistance (Ma et al 2023). Therefore, elucidating the mechanism of chemoresistance in CRC is a hot research topic at home and abroad.…”

Squalene epoxidase promotes the chemoresistance of colorectal cancer via (S)-2,3-epoxysqualene-activated NF-κB

“…5-FU-based adjuvant chemotherapy is recommended for all eligible patients with stage III colon cancer after radical resection, as well as high-risk stage II colon cancer patients (poorly differentiated, T4 tumors, tumor perforation and less than 12 lymph nodes retrieved) [ 4 ]. However, the efficacy of chemotherapy in CRC remains suboptimal, and most CRC patients ultimately develop drug resistance [ 5 ]. In addition, more than 90% of patients diagnosed with metastatic CRC would suffer chemotherapy failure due to drug resistance, and their 5-year survival rate is only 14% [ 5 , 6 ].…”

“…However, the efficacy of chemotherapy in CRC remains suboptimal, and most CRC patients ultimately develop drug resistance [ 5 ]. In addition, more than 90% of patients diagnosed with metastatic CRC would suffer chemotherapy failure due to drug resistance, and their 5-year survival rate is only 14% [ 5 , 6 ]. Therefore, elucidating the mechanism of resistance of CRC to 5-FU is of great significance in designing successful chemotherapy regimens and improving the prognosis of patients with CRC.…”