Drug resistance in targeted cancer therapies with RAF inhibitors

Degirmenci, Ufuk; Yap, Jiajun; Sim, Yuen Rong M.; Qin, Shuang; Hu, Jiancheng

doi:10.20517/cdr.2021.36

Cited by 13 publications

(13 citation statements)

References 187 publications

(365 reference statements)

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“…The genetic alterations that aberrantly activate RAS/RAF/MEK/ERK signaling mainly occur within or upstream of RAF. Nowadays, a breakthrough has been made in the development of RAF inhibitors to treat B-RAF (V600E) mutated cancers ( 44 , 45 ). However, resistance to RAF inhibitors has emerged in subsequent clinical studies, thus researches are trying to look for solutions from natural products.…”

Section: Natural Products Possess Anti-tumor Functionmentioning

confidence: 99%

Remodeling tumor microenvironment with natural products to overcome drug resistance

Zhang

et al. 2022

Front. Immunol.

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With cancer incidence rates continuing to increase and occurrence of resistance in drug treatment, there is a pressing demand to find safer and more effective anticancer strategy for cancer patients. Natural products, have the advantage of low toxicity and multiple action targets, are always used in the treatment of cancer prevention in early stage and cancer supplement in late stage. Tumor microenvironment is necessary for cancer cells to survive and progression, and immune activation is a vital means for the tumor microenvironment to eliminate cancer cells. A number of studies have found that various natural products could target and regulate immune cells such as T cells, macrophages, mast cells as well as inflammatory cytokines in the tumor microenvironment. Natural products tuning the tumor microenvironment via various mechanisms to activate the immune response have immeasurable potential for cancer immunotherapy. In this review, it highlights the research findings related to natural products regulating immune responses against cancer, especially reveals the possibility of utilizing natural products to remodel the tumor microenvironment to overcome drug resistance.

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Section: Natural Products Possess Anti-tumor Functionmentioning

confidence: 99%

Remodeling tumor microenvironment with natural products to overcome drug resistance

Zhang

et al. 2022

Front. Immunol.

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“…Co-expression heat map assesses the correlation between the expression of ERBB2 and gene sets, including the iodine metabolism-related gene set of TSHR , SLC5A8 , SLC26A4 , and TPO ( Portulano et al, 2013 ), the tumor angiogenesis gene set of VEGFA , FLT1 , KDR , FLT4 , PECAM1 , VWF , TIE1 , TEK , ANGPT1 , ANGPT2 , CDH5 , and CLDN5 ( Smith et al, 2010 ; Haibe et al, 2020 ), Lymph node metastasis gene set of EVA1A , TIMP1 , SERPINA1 , FAM20A , FN1 , TNC , and MXRA8 ( Wu et al, 2021 ), distant metastatic gene sets of MMP2 , PTTG1 , VEGFC , CXCR4 , and FGF2 , tumor cell proliferation set of MKI67 , PCNA , and MCM2 ) ( Liang et al, 2011 ), and MEKi resistance marker gene set of SPRY2 , SPRY4 , ETV4 , ETV5 , DUSP4 , DUSP6 , CCND1 , EPHA2 , and EPHA4 ( Mazzoni et al, 2019 ; Degirmenci et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

ERBB2 as a prognostic biomarker correlates with immune infiltrates in papillary thyroid cancer

Jin

Qiu²,

He³

et al. 2022

Front. Genet.

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Epidermal growth factor receptor 2 (ERBB2) is commonly over-expressed in advanced or metastatic tissues of papillary thyroid cancer (PTC) with poor prognosis, while it remains unknown whether ERBB2 plays a role in the progression of PTC. Thus, we analyzed the data derived from online repositories, including TCGA, KEGG, GO, GeneMANIA, and STRING, to explore the relationship between ERBB2 expression and prognosis, tumor phenotypes of interest, and immune infiltrates in PTC. Compared to normal thyroid tissue, ERBB2 was up-regulated in PTC samples (p < 0.001); In comparison with the group with low expression of ERBB2, the group with high expression of ERBB2 had poorer progression-free interval in stage III/IV patients (p = 0.008) and patients aged >45 years (p = 0.019). The up-regulated ERBB2 was associated with iodine metabolism dysfunction, proliferation, metastasis, angiogenesis, and drug resistance. The expression of ERBB2 negatively correlated with enrichment scores of B cells (r = −0.176, p < 0.001), CD8+ T cells (r = −0.160, p < 0.001), cytotoxic cells (r = −0.219, p < 0.001), NK CD56dim cells (r = −0.218, p < 0.001), plasmacytoid dendritic cells (r = −0.267, p < 0.001), T cells (r = −0.164, p < 0.001), T follicular helper cells (r = −0.111, p = 0.012), gamma delta T cells (r = −0.105, p = 0.017), and regulatory T cells (r = −0.125, p = 0.005). In conclusion, ERBB2 may serve as a prognostic biomarker and an immunotherapeutic target in PTC, deserving further exploration.

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“…RAS mutations, which function similarly to RTK alterations, were identified as the second factor downstream of RTKs contributing to RAF inhibitor resistance [ 145 , 146 , 147 , 148 ]. As soon as cancer cells have a large amount of active Ras, the drug-loaded BRAF(V600E) will dimerize with CRAF and activate its catalytic activity [ 149 , 150 ], which has been referred to as the paradoxical effect of RAF inhibitors [ 151 ]. As a result, work is still being carried out on the next iteration of BRAFi.…”

Section: Resistance Mechanismsmentioning

confidence: 99%

Non-Small Cell Lung Cancer Targeted Therapy: Drugs and Mechanisms of Drug Resistance

Lin

2022

IJMS

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The advent of precision medicine has brought light to the treatment of non-small cell lung cancer (NSCLC), expanding the options for patients with advanced NSCLC by targeting therapy through genetic and epigenetic cues. Tumor driver genes in NSCLC patients have been uncovered one by one, including epidermal growth factor receptor (EGFR), mesenchymal lymphoma kinase (ALK), and receptor tyrosine kinase ROS proto-oncogene 1 (ROS1) mutants. Antibodies and inhibitors that target the critical gene-mediated signaling pathways that regulate tumor growth and development are anticipated to increase patient survival and quality of life. Targeted drugs continue to emerge, with as many as two dozen approved by the FDA, and chemotherapy and targeted therapy have significantly improved patient prognosis. However, resistance due to cancer drivers’ genetic alterations has given rise to significant challenges in treating patients with metastatic NSCLC. Here, we summarized the main targeted therapeutic sites of NSCLC drugs and discussed their resistance mechanisms, aiming to provide new ideas for follow-up research and clues for the improvement of targeted drugs.

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Drug resistance in targeted cancer therapies with RAF inhibitors

Cited by 13 publications

References 187 publications

Remodeling tumor microenvironment with natural products to overcome drug resistance

Remodeling tumor microenvironment with natural products to overcome drug resistance

ERBB2 as a prognostic biomarker correlates with immune infiltrates in papillary thyroid cancer

Non-Small Cell Lung Cancer Targeted Therapy: Drugs and Mechanisms of Drug Resistance

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