Colorectal cancer (CRC) is a common malignancy with high morbidity and mortality worldwide. To date, chemotherapy plays an important role in the treatment of CRC patients. Multidrug resistance (MDR) is one of the major hurdles in chemotherapy for CRC, and the underlying mechanisms need to be explored. Studies have demonstrated that Wnt/β‐catenin signaling plays a critical role in oncogenesis and tumor development, and its function in inhibiting apoptosis could facilitate tumor chemoresistance. Recent investigations have also suggested the regulatory effects of the Wnt/β‐catenin signaling pathway in response to chemotherapeutic agents in CRC. Here, we particularly focus on reviewing the evidences suggesting the mechanisms of Wnt/β‐catenin signaling in the chemoresistance modulation of colorectal cancer.

• Our research confirmed that luteolin could attenuate the chemoresistance of osteosarcoma through inhibiting the PTN/β-catenin/MDR1 signaling axis by upregulating miR-384. • Our study demonstrated that doxorubicin resistance could be inhibited by the transfer of exosomal miR-384 into recipient chemoresistant osteosarcoma cells. • The in vivo experiment showed combination therapy with both doxorubicin and luteolin resulted in higher survival rates compared with other single–agent therapies.

Despite the advances made in cancer treatment in the past decades, therapeutic efficacy is still quite challenging, partially due to the emergence of multidrug resistance (MDR). It is crucial to decipher the underlying mechanisms of resistance in order to develop new therapeutic strategies for cancer patients. Previous studies have shown that activation of nuclear factor-κB (NF-κB) plays key roles in various cellular processes including proliferation, anti-apoptosis, metastasis, invasion, and chemoresistance. In this review, we conduct an integrated analysis of the evidence suggesting the vital roles of the NFκB signaling pathway in MDR during chemotherapy, immunotherapy, endocrine and targeted therapy. A literature search was performed on NFκB and drug resistance in PubMed up to Feb 2023. This review summarizes that the NF-κB signaling pathway exhibits a crucial role in enhancing drug resistance in chemotherapy, immunotherapy, endocrine and targeted therapy. The application of combination therapy with existing antineoplastic drugs and a safe NF-κB inhibitor could become a promising strategy in cancer treatment. A better understanding of the pathway and mechanisms of drug resistance may help exploit safer and more effective NF-κB-targeting agents for clinical use in the future.

Colorectal cancer (CRC) is a commonly diagnosed digestive malignancy worldwide. Ras-related protein 1A (RAP1A) is a member of the Ras superfamily of small GTPases and has been recently identified as a novel oncoprotein in several human malignancies. However, its specific role in CRC remains unclear. In this study, we firstly analyzed its expression and clinical significance in a retrospective cohort of 144 CRC patients. Then, cellular assays in vitro and in vivo were performed to clarify its biological role in CRC cells. Finally, microarray analysis was utilized to investigate the molecular mechanisms regulated by RAP1A in CRC progression. Firstly, RAP1A expression was abnormally higher in CRC tissues as compared with adjacent normal tissues, and significantly correlated tumor invasion. High RAP1A expression was an independent unfavourable prognostic factor for CRC patients. Combining RAP1A expression and preoperative CEA level contributed to a more accurate prognostic stratification in CRC patients. Secondly, knockdown of RAP1A dramatically inhibited the growth of CRC cells, while it was opposite for RAP1A overexpression. Finally, the microarray analysis revealed RAP1A promoted CRC growth partly through phosphatase and tensin homolog (PTEN)/forkhead box O3(FOXO3)/cyclin D1(CCND1) signaling pathway. FOXO3 overexpression could partly mimic the inhibitory effect of RAP1A knockdown in CRC growth. Moreover, FOXO3 overexpression inhibited CCND1 expression, but had no impact on RAP1A and PTEN expression. RAP1A promotes CRC development partly through PTEN/FOXO3 /CCND1 signaling pathway. It has a great potential to be an effective clinical biomarker and therapeutic target for CRC patients.

Breast cancer is a prevalent malignancy worldwide, and its treatment has increasingly shifted towards precision medicine, with immunotherapy emerging as a key therapeutic strategy. Deubiquitination, an essential epigenetic modification, is regulated by deubiquitinating enzymes (DUBs) and plays a critical role in immune function and tumor progression. Ubiquitin-specific proteases (USPs), a prominent subgroup of DUBs, are involved in regulating immune cell functions, antigen processing, and T cell development in the context of breast cancer. Certain USPs also modulate the differentiation of immune cells, such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), within the breast cancer immune microenvironment. Furthermore, several USPs influence the expression of PD-L1, thus affecting the efficacy of immune checkpoint inhibitors. The overexpression of USPs may promote immune evasion, contributing to the development of treatment resistance. This review elucidates the role of USPs in modulating the immune microenvironment and immune responses in breast cancer. Additionally, it discusses effective strategies for combining USP inhibitors with other therapeutic agents to enhance treatment outcomes. Therefore, targeting USPs presents the potential to enhance the efficacy of immunotherapy and overcome drug resistance, offering a more effective treatment strategy for breast cancer patients.