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Colorectal cancer (CRC) is one of the most frequently occurring primary malignant tumors worldwide. Chemotherapeutic resistance is a major clinical problem in the treatment of CRC. Therefore, it is of great importance to investigate novel biomarkers that may predict chemoresistance and facilitate the development of individualized treatment for patients with CRC. The present study reported that let‑7f‑5p expression was elevated in chemotherapy‑resistant CRC tissues compared with chemotherapy‑sensitive tissues. Furthermore, upregulating let‑7f‑5p increased the expression levels of the anti‑apoptotic proteins, B‑cell lymphoma 2 (Bcl‑2) and B‑cell lymphoma‑extra large (Bcl‑xL), and decreased the activity of caspase‑3 and caspase‑9 in CRC cells. By contrast, downregulating let‑7f‑5p yielded the opposite effect. Notably, the results indicated that let‑7f‑5p promoted chemotherapeutic resistance by directly repressing the expression of several pro‑apoptotic proteins, including tumor protein p53, tumor protein p53‑inducible nuclear protein 1, tumor protein p53‑inducible nuclear protein 2 and caspase‑3. Therefore, a novel mechanism by which let‑7f‑5p enhances the resistance of CRC cells to chemotherapeutics has been revealed, indicating that silencing let‑7f‑5p may become an effective therapeutic strategy against CRC. [ABSTRACT FROM AUTHOR]

Interaction between the programmed cell death ligand 1 (PD‑L1) and programmed cell death 1 (PD‑1) contributes to tumor cell resistance to chemotherapeutic agents. PD‑L1 is expressed in the cells of diffuse large B‑cell lymphoma (DLBCL), one common type of malignant non‑Hodgkin lymphomas. However, little is known about how the PD‑1/PD‑L1 pathway functions in the pathogenesis of DLBCL. Therefore, the present study investigated whether and how the PD‑1/PD‑L1 axis is involved in regulating the sensitivity of CRL2631, a DLBCL cell line, to the CHOP (Cyclophosphamide, Hydroxydaunorubicin/adriamycin, Oncovin/vincristine and Prednisone) chemotherapeutic regimen. CHOP treatment significantly decreased cell survival rate and increased apoptosis in CRL2631 cells. The application of recombinant human PD‑1 (rPD‑1) significantly decreased the cytotoxic effects of the CHOP regimen in CRL2631 cells, but not in the CRL2631 cells with PD‑L1 deficiency. In the CRL2631 cells, rPD‑1 enhanced the activity of the phosphoinositide 3‑kinase (PI3K)/protein kinase B (Akt1) pathway. However, the activity level of the PI3K/Akt1 pathway was decreased in CHOP‑treated CRL2631 cells. The selective PI3K inhibitor BKM120 significantly increased CHOP‑induced apoptosis, but this effect was abolished by rPD‑1 and aggravated by PD‑L1 knockdown. In CHOP‑treated PD‑L1 knockdown cells, the increased apoptosis was markedly inhibited by the overexpression of constitutively active Akt1. Overall, the results demonstrate that the over‑activated PD‑1/PD‑L1 axis is associated with chemotherapeutic resistance of DLBCL cells to the CHOP regimen, potentially through a PI3K‑dependent mechanism. [ABSTRACT FROM AUTHOR]

Drug resistance is a primary cause of chemotherapeutic failure; however, how this resistance develops is complex. A comprehensive understanding of chemotherapeutic resistance mechanisms may aid in identifying more effective drugs and improve the survival rates of patients with cancer. Insulin-like growth factor 1 receptor (IGF1R), a member of the insulin receptor family, has been extensively assessed for biological activity, and its putative contribution to tumor cell development and progression. Furthermore, researchers have attended to drugs that target IGF1R since IGF1R functions as a membrane receptor. However, how IGF1R participates in chemotherapeutic resistance remains unclear. Therefore, the present study described the IGF1R gene and its associated signaling pathways, and offered details of IGF1R-induced tumor chemoresistance associated with promoting cell proliferation, inhibition of apoptosis, regulation of ATP-binding cassette transporter proteins and interactions with the extracellular matrix. The present study offered additional explanations for tumor chemotherapy resistance and provided a theoretical basis of IGF1R and its downstream pathways for future possible chemotherapy treatment options. [ABSTRACT FROM AUTHOR]

At present, one of the major problems of cancer therapy is drug resistance. Breast cancer resistance protein (BCRP), a marker of the multidrug-resistant phenotype, affects drug absorption, distribution, metabolism, and excretion in normal tissues. Meanwhile, extracellular vesicles (EVs) have attracted increasing attention as a medium of cell-to-cell communication. However, the association between BCRP and circulating EVs remains unclear. The present study demonstrated that patients who did not respond or had progressive/ stable disease following chemotherapy had markedly higher BCRP levels compared to those that did not receive chemotherapy. Moreover, BCRP was upregulated at the mRNA and protein levels in tumor-derived circulating EVs from patients with a poor response to chemotherapy. Interestingly, the results also demonstrated that BCRP was co-expressed with MUC1, which is frequently expressed in breast cancer and is exported via EVs, and both BCRP and MUC1 were up-regulated after chemotherapy. In conclusion, the present study indicates that tumor-derived circulating EVs that carry BCRP may serve as a predictive biomarker of the response to chemotherapy for breast cancer. In addition, the results provide a window for individualized treatment to overcome resistance to chemotherapeutic drugs. [ABSTRACT FROM AUTHOR]

Capecitabine is a chemotherapeutic drug used in patients with breast, colon and gastric cancer. Hand-foot syndrome (HFS) is a type of dermatitis that frequently occurs as a reaction to capecitabine. To date, no effective strategies have been found to prevent or reverse HFS. Furthermore, chemotherapy induces an elevation in the expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), and this activation represents a critical mechanism for the induction of chemotherapeutic resistance. Adapalene is a third-generation synthetic retinoid. Topical retinoids are important therapeutic anti-aging agents for managing photo-damaged skin, and are known to increase HB-EGF levels, which is important for skin wound healing. Accordingly, the current report focused on the topical retinoids that increase HB-EGF expression in the skin, and we hypothesized that these topical retinoids induce local chemotherapeutic resistance in the skin of patients receiving chemotherapy and consequently, decrease the cutaneous side-effects of chemotherapy. This report presents a case of the successful treatment of refractory HFS induced by capecitabine using the topical application of adapalene. Topical adapalene was applied for 3 months and significantly reduced inflammation and pain following chemotherapy. Topical retinoids may have the potential to effectively treat capecitabine-induced HFS by increasing HB-EGF expression and decreasing cutaneous side-effects. Further studies are required to establish the therapeutic efficacy of topical retinoids on HFS. [ABSTRACT FROM AUTHOR]