☆ 4.7 Review

A Brief Review on Chemoresistance; Targeting Cancer Stem Cells as an Alternative Approach

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2023)

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Article Biochemical Research Methods

Activation of Wnt/β-Catenin signaling in EpCAMhigh/CD44+ cells endow colorectal cancer with tumor proliferation and oxaliplatin chemoresistance

Fengqiang Zhou et al.

COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING (2023)

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Article Oncology

Molecular tests for prediction of tumor sensitivity to cytotoxic drugs

Evgeny N. Imyanitov et al.

Summary: Chemotherapy is the mainstay of cancer treatment, with predictive assays helping to personalize drug administration. Genetic deficiencies can impact tumor responsiveness to certain drugs, allowing for dosage adjustment through pharmacogenetic testing. Promising molecular predictors may lead to new clinically useful markers for cytotoxic therapy.

CANCER LETTERS (2022)

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Article Genetics & Heredity

miR-197-5p increases Doxorubicin-mediated anticancer cytotoxicity of HT1080 fibrosarcoma cells by decreasing drug efflux

Neha Jain et al.

Summary: In this study, researchers aimed to investigate the combined application of miR-197-5p and Doxorubicin (Dox) in enhancing the sensitivity of fibrosarcoma cells to Dox and improving its anti-tumor effects. Through a series of experiments, they found that miR-197-5p increased the sensitivity of HT1080 fibrosarcoma cells to Dox by promoting apoptosis and G2/M cell cycle arrest, and by suppressing MDR genes to increase drug influx. Additionally, they observed that the target protein of miR-197-5p, KIAA0101, was inhibited by Dox and further repressed when treated in combination with the miRNA. The combination treatment also led to an upregulation of p53, which is negatively correlated with KIAA0101, compared to Dox alone.

DNA REPAIR (2022)

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Article Biochemistry & Molecular Biology

Structure-Function Relationships in the Human P-Glycoprotein (ABCB1): Insights from Molecular Dynamics Simulations

Liadys Mora Lagares et al.

Summary: P-gp is an important protein involved in drug efflux and multidrug resistance. Molecular dynamics simulations can provide valuable insights into the binding behavior and conformational changes of P-gp in the presence of different compounds.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Biochemistry & Molecular Biology

Expression and Functional Contribution of Different Organic Cation Transporters to the Cellular Uptake of Doxorubicin into Human Breast Cancer and Cardiac Tissue

Marcus Otter et al.

Summary: Transporter proteins play a crucial role in the efficacy and toxicity of doxorubicin, and genetic and environmental factors contribute to the variability in their expression and function.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Medicine, Research & Experimental

Induction of cancer cell stemness in glioma through glycolysis and the long noncoding RNA HULC-activated FOXM1/AGR2/HIF-1α axis

You-Ping Li et al.

Summary: This study identifies a novel therapeutic target for glioma, highlighting the role of the long noncoding RNA highly upregulated in liver cancer (HULC). HULC stabilizes Forkhead box M1 (FOXM1) to upregulate the expression of anterior gradient 2 (AGR2) and hypoxia-inducible factor-1 alpha (HIF-1 alpha), promoting glycolysis and stemness in glioma stem cells (GSCs) and accelerating the development of glioma.

LABORATORY INVESTIGATION (2022)

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Article Biochemistry & Molecular Biology

Caspase-2 regulates S-phase cell cycle events to protect from DNA damage accumulation independent of apoptosis

Ashley G. Boice et al.

Summary: The study demonstrates that caspase-2 is activated in dividing cells in G1 phase of the cell cycle and plays a crucial role in maintaining genomic stability by protecting cells from replication stress and promoting replication fork protection. These functions are independent of its pro-apoptotic role and involve regulating cell cycle and DNA repair events to prevent the accumulation of DNA damage.

ONCOGENE (2022)

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Article Pharmacology & Pharmacy

Deregulation of the CD44-NANOG-MDR1 associated chemoresistance pathways of breast cancer stem cells potentiates the anti-cancer effect of Kaempferol in synergism with Verapamil

Tanaya Roychowdhury et al.

Summary: Chemoresistance is a challenge in breast cancer treatment, and this study investigates the mechanism behind it and its inhibition using specific drugs. The combination of Kaempferol (K) and Verapamil (V), an inhibitor of MDR1, effectively inhibits the survival of breast cancer stem cells (BCSC) and reduces the expression levels of candidate genes.

TOXICOLOGY AND APPLIED PHARMACOLOGY (2022)

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Article Cell Biology

TFEB Regulates ATP7B Expression to Promote Platinum Chemoresistance in Human Ovarian Cancer Cells

Raffaella Petruzzelli et al.

Summary: ATP7B is a key player in the regulation of copper homeostasis and signaling as well as chemoresistance in cancer. This study found that transcription factor EB (TFEB) binds to specific regions of ATP7B, promoting its transcription and contributing to drug resistance in cancer cells.

CELLS (2022)

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Review Cell Biology

It's Getting Complicated-A Fresh Look at p53-MDM2-ARF Triangle in Tumorigenesis and Cancer Therapy

Che-Pei Kung et al.

Summary: The relationship between P53, MDM2, and ARF plays a crucial role in tumor suppression mechanisms, but our understanding of this relationship needs to be updated in order to develop more effective cancer treatments.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Article Oncology

Inhibiting nonhomologous end-joining repair would promote the antitumor activity of gemcitabine in nonsmall cell lung cancer cell lines

Nannan Guo et al.

Summary: The combination of Ku70/80 heterodimer protein inhibitor STL127705 and gemcitabine was found to enhance the sensitivity of NSCLC cell lines to irradiation and induce apoptosis. This combination treatment effectively inhibits the NHEJ pathway and enhances DNA damage, leading to tumor cell death.

ANTI-CANCER DRUGS (2022)

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Article Biochemical Research Methods

Metabolomics analysis reveals Oct4 overexpression drives metabolic reprogramming and enhanced glycolysis and pentose phosphate pathway in lung adenocarcinoma cells

Yabin Tang et al.

Summary: Poor prognosis in lung adenocarcinoma is linked to metabolic reprogramming driven by Oct4 overexpression, which could serve as a potential therapeutic target and diagnostic strategy for the treatment of this disease.

BIOMEDICAL CHROMATOGRAPHY (2022)

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Article Medicine, Research & Experimental

CDX2 controls genes involved in the metabolism of 5-fluorouracil and is associated with reduced efficacy of chemotherapy in colorectal cancer

Jean-Baptiste Delhorme et al.

Summary: This study demonstrates the role of CDX2 in chemoresistance of CRC, showing that CDX2 expression enhances resistance of colon cancer cells towards 5-FU by regulating ABCC11 and DPYD genes. The findings suggest the therapeutic potential of targeting CDX2/ABCC11/DPYD pathway to improve systemic chemotherapy in CRC.

BIOMEDICINE & PHARMACOTHERAPY (2022)

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Article Oncology

IL-10 contributes to gemcitabine resistance in extranodal NK/T-cell lymphoma cells via ABCC4

Jia Huo et al.

Summary: The study revealed that IL-10 contributes to the resistance of ENKTL cells via ABCC4 and regulates the JAK/STAT signaling pathway. Serum IL-10 levels were higher in ENKTL patients, and IL-10 weakened the effects of gemcitabine on cell killing, cell cycle arrest, and apoptosis promotion.

INVESTIGATIONAL NEW DRUGS (2022)

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Article Oncology

Circular RNA circ-MTHFD1L induces HR repair to promote gemcitabine resistance via the miR-615-3p/RPN6 axis in pancreatic ductal adenocarcinoma

Zhi-Wen Chen et al.

Summary: This study found that circ-MTHFD1L maintains chemoresistance to gemcitabine in PDAC through the miR-615-3p/RPN6 signaling axis. The results suggest that circ-MTHFD1L may serve as a molecular marker for effective treatment of PDAC.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2022)

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Article Oncology

MiRNA-363-3p/DUSP10/JNK axis mediates chemoresistance by enhancing DNA damage repair in diffuse large B-cell lymphoma

Wenping Zhou et al.

Summary: The miRNA-363-3p/DUSP10/JNK axis is a novel chemoresistance mechanism in DLBCL, and high expression of miRNA-363-3p is associated with chemoresistance. Targeting the miRNA-363-3p/DUSP10/JNK axis can inhibit DNA repair pathways and improve the effectiveness of chemotherapy.

LEUKEMIA (2022)

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Article Oncology

Inflammatory bowel disease induces inflammatory and pre-neoplastic changes in the prostate

Anuj S. Desai et al.

Summary: The study found that men with IBD had a higher proportion of T and B lymphocyte infiltration in prostate tumors. Mouse models showed that chronic colitis can be transferred to the wild-type mouse prostate, causing abnormal levels of pro-inflammatory cytokines and oncogenic signaling activation.

PROSTATE CANCER AND PROSTATIC DISEASES (2022)

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Article Multidisciplinary Sciences

Blockade of p38 MAPK overcomes AML stem cell line KG1a resistance to 5-Fluorouridine and the impact on miRNA profiling

Sabine Matou-Nasri et al.

Summary: This study emphasizes the key role of the p38 MAPK survival pathway in chemoresistance capacity of AML stem cells and the potential involvement of miRNAs, which may pave the way for the development of new therapeutic strategies targeting survival signaling proteins and reducing the rate of AML relapse.

PLOS ONE (2022)

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Article Oncology

Expression status of p53 and organic cation transporter 1 is correlated with poor response to preoperative chemotherapy in esophageal squamous cell carcinoma

Masahiro Izutsu et al.

Summary: The study suggests that the expression of p53(MT-ex) or OCT1(Low) in pretreatment biopsy specimens may be potential predictors of poor response to preoperative chemotherapy with CF-based regimens in ESCC, although specificity needs improvement.

WORLD JOURNAL OF SURGICAL ONCOLOGY (2022)

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Article Multidisciplinary Sciences

Cancer genomic profiling identified dihydropyrimidine dehydrogenase deficiency in bladder cancer promotes sensitivity to gemcitabine

Shigehiro Tsukahara et al.

Summary: This study investigates the genomic landscape of muscle-invasive bladder cancer (MIBC) in relation to chemotherapy response and explores the biological role of genomic alterations. The study finds that DPYD genomic alterations and DPD expression are potential predictive biomarkers in gemcitabine treatment for MIBC.

SCIENTIFIC REPORTS (2022)

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Article Medicine, Research & Experimental

miR-6077 promotes cisplatin/pemetrexed resistance in lung adenocarcinoma via CDKN1A/cell cycle arrest and KEAP1/ferroptosis pathways

Guoshu Bi et al.

Summary: The study identified miR-6077 as a key driver of cisplatin/pemetrexed resistance in lung adenocarcinoma (LUAD). Overexpression of miR-6077 desensitized LUAD cells to cisplatin/pemetrexed by affecting cell cycle and ferroptosis, leading to cell death. This research provides a novel therapeutic strategy for overcoming chemoresistance in clinical practice.

MOLECULAR THERAPY-NUCLEIC ACIDS (2022)

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Article Oncology

Transient Receptor Potential Cation Channel Subfamily V Member 1 Expression Promotes Chemoresistance in Non-Small-Cell Lung Cancer

Li Li et al.

Summary: TRPV1 is overexpressed in non-small-cell lung cancer, and its overexpression leads to increased resistance to DDP and 5-FU. TRPV1 mediates chemoresistance by increasing drug efflux, enhancing DNA repair pathways, and promoting cell survival.

FRONTIERS IN ONCOLOGY (2022)

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Article Oncology

S100A14: A novel negative regulator of cancer stemness and immune evasion by inhibiting STAT3-mediated programmed death-ligand 1 expression in colorectal cancer

Hye-Young Min et al.

Summary: This study identified a novel function of S100A14 (SA14) in colorectal cancer (CRC) by regulating programmed death-ligand 1 (PD-L1) expression, impacting cancer stem-like cell (CSC) phenotypes and chemoresistance. SA14 may serve as a predictive biomarker for anti-PD-L1 immunotherapy and chemotherapy in combination treatment.

CLINICAL AND TRANSLATIONAL MEDICINE (2022)

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Article Oncology

3D matrix promotes cell dedifferentiation into colorectal cancer stem cells via integrin/cytoskeleton/glycolysis signaling

Tong Han et al.

Summary: This study provides evidence that colorectal cancer cells can dedifferentiate to cancer stem cells and regain stem-like properties when cultured in the presence of extracellular matrix reagents. The 3D extracellular matrix mediates cytoskeletal changes, which contribute to the release of a protein and the degradation of an enzyme, resulting in enhanced glycolysis and upregulation of a transcription factor, ultimately promoting tumor progression.

CANCER SCIENCE (2022)

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Article Cell Biology

PI3K/AKT signaling allows for MAPK/ERK pathway independency mediating dedifferentiation-driven treatment resistance in melanoma

Eyleen Corrales et al.

Summary: This study comprehensively characterized a panel of patient-derived BRAFV600E positive melanoma cell lines and found that a decrease in sensitivity to MAPK/ERK pathway inhibition corresponded with increased migratory potential and the acquisition of stem cell-like properties. Additionally, it was discovered that increased activity of the PI3K/AKT pathway lead to a decreased dependency on MAPK/ERK signaling in melanoma cells.

CELL COMMUNICATION AND SIGNALING (2022)

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Review Biochemistry & Molecular Biology

Dual Role of Fibroblasts Educated by Tumour in Cancer Behavior and Therapeutic Perspectives

Belen Toledo et al.

Summary: Tumours are complex systems consisting of dynamic interactions between tumour cells, non-tumour cells, and extracellular components that make up the tumour microenvironment (TME). Cancer-associated fibroblasts play a crucial role in extracellular matrix construction, tumour metabolism, immunology, adaptive chemoresistance, and tumour cell motility. The interaction between CAFs and tumour cells has shifted the focus from considering stromal cells as mere physical support to recognizing their importance in the tumour process.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Review Medicine, Research & Experimental

Signaling pathways in the regulation of cancer stem cells and associated targeted therapy

Wang Manni et al.

Summary: This review provides an overview of the regulating networks and immune interactions involved in CSC development, and discusses the latest advances in CSC-directed therapeutics.

MEDCOMM (2022)

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Article Dentistry, Oral Surgery & Medicine

Overexpression of RRM2 is related to poor prognosis in oral squamous cell carcinoma

Shuo Wang et al.

Summary: The overexpression of RRM2 in oral squamous cell carcinoma is associated with disease progression, recurrence, and poor prognosis. RRM2 expression promotes cancer cell proliferation and migration while inhibiting apoptosis. This suggests that RRM2 could be a potential target for diagnosis, prognosis, and therapy of OSCC.

ORAL DISEASES (2021)

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Article Biochemistry & Molecular Biology

Mammalian dihydropyrimidine dehydrogenase

Dariush C. Forouzesh et al.

Summary: DPD catalyzes the reduction of pyrimidine bases using a complex cofactor set, including flavins and iron-sulfur centers. The enzyme has two active sites that interact with NADPH, pyrimidine substrates, and form an electron transfer wire. DPD accepts 5-fluorouracil as a substrate and affects toxicity.

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS (2021)

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Article Oncology

APR-246 induces apoptosis and enhances chemo-sensitivity via activation of ROS and TAp73-Noxa signal in oesophageal squamous cell cancer with TP53 missense mutation

Teruyuki Kobayashi et al.

Summary: Mutations in the p53 gene are found in 90% of esophageal squamous cell carcinoma (ESCC) patients, and APR-246 shows potential as a therapeutic agent to overcome chemo-resistance by inducing apoptosis through restoring transcriptional ability of mutant p53. APR-246 treatment induces significant apoptosis in ESCC cell lines with p53 missense mutations by upregulating p73 and Noxa via ROS induction, and the combination with chemotherapy enhances antitumor effects.

BRITISH JOURNAL OF CANCER (2021)

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Article Oncology

Hypoxia Drives Dihydropyrimidine Dehydrogenase Expression in Macrophages and Confers Chemoresistance in Colorectal Cancer

Marie Malier et al.

Summary: The study reveals that macrophages specifically overexpress DPD in hypoxia, leading to macrophage-induced chemoresistance to 5-FU, while tumor cells do not express significant levels of DPD. These findings shed light on the crucial role of TAMs in promoting chemoresistance in colorectal cancers.

CANCER RESEARCH (2021)

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Review Genetics & Heredity

MicroRNAs and the DNA damage response: How is cell fate determined

Hartwig Visser et al.

Summary: The DNA damage response plays a crucial role in determining cell fate, with miRNAs potentially influencing cell fate by regulating key DDR proteins. While miRNAs are dysregulated in cancerous tissues, further research is needed to establish their functional association in this context.

DNA REPAIR (2021)

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Article Genetics & Heredity

CometChip enables parallel analysis of multiple DNA repair activities

Jing Ge et al.

Summary: DNA damage is directly linked to aging, cancer, and other diseases, and cells have evolved highly conserved DNA repair pathways to counteract its deleterious effects. The CometChip platform offers increased throughput and sensitivity for parallel analysis of multiple DNA repair activities, expanding the utility of the comet assay for precise, high-throughput assessment of repair deficiencies in different pathways.

DNA REPAIR (2021)

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Letter Oncology

m6A regulators as predictive biomarkers for chemotherapy benefit and potential therapeutic targets for overcoming chemotherapy resistance in small-cell lung cancer

Zhihui Zhang et al.

Summary: Small-cell lung cancer (SCLC) is typically treated with platinum-based chemotherapy as first-line therapy, but drug resistance is common. Researchers have identified the predictive value and potential therapeutic targets of N-6-methyladenosine (m(6)A) in SCLC patients, providing new insights into overcoming chemotherapy resistance.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2021)

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Article Medicine, Research & Experimental

FOXM1 inhibitor, Siomycin A, synergizes and restores 5-FU cytotoxicity in human cholangiocarcinoma cell lines via targeting thymidylate synthase

Nathakan Klinhom-On et al.

Summary: The study demonstrated that the FOXM1 inhibitor Siomycin A enhances 5-FU cytotoxicity and reverses 5-FU resistance in cholangiocarcinoma cell lines, providing a new strategy to overcome 5-FU resistance.

LIFE SCIENCES (2021)

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Article Oncology

Roles for hENT1 and dCK in gemcitabine sensitivity and malignancy of meningioma

Masahiro Yamamoto et al.

Summary: The study found that hENT1 and dCK expression levels in high-grade meningioma cells are closely related to tumor cell proliferative activity and patient survival. These results highlight the critical roles of hENT1 and dCK in the growth and gemcitabine sensitivity of meningioma cells.

NEURO-ONCOLOGY (2021)

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Article Oncology

Dysregulated APOBEC3G causes DNA damage and promotes genomic instability in multiple myeloma

Srikanth Talluri et al.

Summary: The study revealed a crucial role of APOBEC/AID in multiple myeloma, leading to genomic instability, with APOBEC3G being a prominent mutational signature at diagnosis and relapse, significantly contributing to DNA damage and mutational changes in MM cells. These findings highlight APOBEC3G as a novel gene impacting genomic evolution and underlying mechanisms in MM.

BLOOD CANCER JOURNAL (2021)

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Article Oncology

Atypical cyclin P regulates cancer cell stemness through activation of the WNT pathway

Abril Sanchez-Botet et al.

Summary: Experimental findings reveal that CCNP plays a crucial role in cancer stem cell characteristics, including promoting sphere formation, enhancing the expression of stemness and pluripotency markers, inducing resistance to anticancer drugs, and activating the WNT pathway.

CELLULAR ONCOLOGY (2021)

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Review Cell Biology

Mutant p53 Gain-of-Function: Role in Cancer Development, Progression, and Therapeutic Approaches

Eduardo Alvarado-Ortiz et al.

Summary: Frequent p53 mutations not only abolish tumor suppressor capacities but also confer various gain-of-function activities that impact key pathways in tumor development and progression. The effects of these mutations on proliferation, migration, metabolic reprogramming, and immune evasion constitute major driving forces for human tumors. The interaction of mutp53 with molecules such as AMPK and SREBP1 leads to metabolic reprogramming and favors anabolic pathways in cancer cells.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Article Oncology

Deciphering the Role of Intestinal Crypt Cell Populations in Resistance to Chemotherapy

Carla Frau et al.

Summary: The study reveals paradoxical roles of MSI1 in both facilitating intestinal regeneration after injury and promoting drug-resistant colorectal cancer stem cells. Increased levels of MSI1 contribute to the reprogramming of progenitor cells into drug-resistant phenotypes, highlighting its importance in chemotherapy resistance and tumor grading in colorectal cancer patients. These findings shed light on the biology and plasticity of normal and cancer cell populations, presenting potential new targets for improving chemotherapy outcomes.

CANCER RESEARCH (2021)

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Article Pharmacology & Pharmacy

Elevated N-Glycosylation Contributes to the Cisplatin Resistance of Non-Small Cell Lung Cancer Cells Revealed by Membrane Proteomic and Glycoproteomic Analysis

Wenjuan Zeng et al.

Summary: Chemoresistance to cisplatin is closely related to aberrant changes in protein glycosylation. This study utilized proteomic and N-glycoproteomic methods to comprehensively characterize cisplatin resistance-related membrane proteins in non-small cell lung cancer cells. The findings indicate that alterations in protein abundance and glycosylation levels are associated with the development of cisplatin resistance, impacting cell migration and invasion ability, as well as intracellular drug accumulation.

FRONTIERS IN PHARMACOLOGY (2021)

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Review Cell Biology

Mutant p53 in cell-cell interactions

Steven Pilley et al.

Summary: p53 is a crucial tumor suppressor gene, and mutations in p53 can impact cancer development and progression. In addition to its cell-autonomous functions, the status of p53 can also influence the interactions between cancer cells.

GENES & DEVELOPMENT (2021)

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Review Oncology

Beyond the Double-Strand Breaks: The Role of DNA Repair Proteins in Cancer Stem-Cell Regulation

Jacqueline Nathansen et al.

Summary: Cancer stem cells (CSCs) are a highly tumorigenic cell population capable of repopulating tumors and causing relapses even after successful therapy. They possess enhanced DNA repair mechanisms that not only contribute to therapy resistance, but also play crucial roles in tumor evolution and treatment resistance. The role of DNA repair proteins in CSCs extends beyond DNA repair, impacting transcription regulation, signaling pathways, cellular stress responses, and immune reactions towards tumor cells. Targeting DNA repair pathways in CSCs holds promise for personalized therapies and sensitizing CSCs to anti-cancer treatments.

CANCERS (2021)

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Article Oncology

The ZEB2-dependent EMT transcriptional programme drives therapy resistance by activating nucleotide excision repair genes ERCC1 and ERCC4 in colorectal cancer

Rahul Sreekumar et al.

Summary: In patients with colorectal cancer, ZEB2 is a biomarker predicting tumor response to chemotherapy and risk of recurrence. The ZEB2-dependent EMT transcriptional program enhances CRC cell viability to oxaliplatin treatment by activating the NER pathway.

MOLECULAR ONCOLOGY (2021)

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Article Biochemistry & Molecular Biology

NSMF promotes the replication stress-induced DNA damage response for genome maintenance

Min Kyung Ju et al.

Summary: Proper activation of the DNA repair pathways in response to DNA replication stress is crucial for maintaining genomic integrity. NSMF has been identified as a key factor in the replication stress response, regulating the ATR pathway and contributing to genome stability and cell survival.

NUCLEIC ACIDS RESEARCH (2021)

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Review Oncology

Possibility of inducing tumor cell senescence during therapy

Guohui Wang et al.

Summary: Treatment options for cancer include surgery, radiotherapy, and chemotherapy, but high-dose chemotherapy can have toxic side effects and lead to drug resistance. Cellular senescence is activated by various pathways and may inhibit the occurrence and development of tumors.

ONCOLOGY LETTERS (2021)

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Article Cell Biology

The lack of functional DNMT2/TRDMT1 gene modulates cancer cell responses during drug-induced senescence

Dominika Bloniarz et al.

Aging-US (2021)

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Article Medicine, Research & Experimental

Colossolactone-G synergizes the anticancer properties of 5-fluorouracil and gemcitabine against colorectal cancer cells

Rinad A. Algehani et al.

Summary: A synergistic effect in terms of anticancer properties was observed when colossolactone-G was combined with 5-FU and GCB, influencing both apoptosis and autophagic cell death mechanisms.

BIOMEDICINE & PHARMACOTHERAPY (2021)

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Article Oncology

Pharmacokinetics of preoperative intraperitoneal 5-FU in patients with pancreatic ductal adenocarcinoma

Mikael oman et al.

Summary: This study investigated the pharmacokinetics of preoperatively administered intraperitoneal 5-FU in patients with resectable PDAC by analyzing levels of 5-FU and metabolites in different tissues. The results showed uptake of 5-FU and drug metabolism to active FdUMP in pancreatic tumor, liver, and lymph nodes, with potential correlations between gene expression and metabolite concentrations. Further studies are needed to evaluate the IP route for 5-FU administration in PDAC patients.

CANCER CHEMOTHERAPY AND PHARMACOLOGY (2021)

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Article Biochemistry & Molecular Biology

BCL-XL is crucial for progression through the adenoma-to-carcinoma sequence of colorectal cancer

Prashanthi Ramesh et al.

Summary: The study suggests a shift in antiapoptotic protein reliance in the progression of colorectal cancer, with BCL-2 being essential during ISC transformation and BCL-XL playing a crucial role in stem cell survival from adenoma to carcinoma. Targeting BCL-XL may enhance the efficacy of chemotherapy in CRC management.

CELL DEATH AND DIFFERENTIATION (2021)

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Article Biochemistry & Molecular Biology

DNA damage and oxidant stress activate p53 through differential upstream signaling pathways

Tao Shi et al.

Summary: Oxidizing conditions trigger activation of the p53 tumor suppressor, with contributions from both SAPK signaling and DNA damage signaling pathways depending on the type of oxidant used. Modulating oxidative signaling could potentially stimulate p53 without inducing collateral DNA damage, thus limiting mutation accumulation in both healthy and tumor tissues.

FREE RADICAL BIOLOGY AND MEDICINE (2021)

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Article Biochemistry & Molecular Biology

Ganciclovir and Its Hemocompatible More Lipophilic Derivative Can Enhance the Apoptotic Effects of Methotrexate by Inhibiting Breast Cancer Resistance Protein (BCRP)

Magdalena Markowicz-Piasecka et al.

Summary: The study investigated the inhibition of efflux transporters by GCV and its derivative on MTX in human breast cancer cells. It was found that both compounds enhanced the cellular accumulation of MTX, leading to reduced number of viable cells and increased late apoptotic cells. The improved apoptotic effects with higher MTX exposure were mainly attributed to the inhibition of BCRP-mediated efflux of MTX.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Pharmacology & Pharmacy

Zebularine suppressed gemcitabine-induced senescence and improved the cellular and plasma pharmacokinetics of gemcitabine, augmented by liposomal co-delivery

Mingtan Tang et al.

Summary: This study investigated the potential of using zebularine in combination with a nanomedicine co-delivery approach to overcome gemcitabine-resistance in pancreatic cancer cells. Zebularine was found to suppress the regrowth of senescent cells and enhance cellular gemcitabine concentration. Co-delivery of zebularine with liposomes increased cellular gemcitabine concentration and extended the half-life of gemcitabine in plasma.

INTERNATIONAL JOURNAL OF PHARMACEUTICS (2021)

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Article Chemistry, Multidisciplinary

Co-Delivery Using pH-Sensitive Liposomes to Pancreatic Cancer Cells: the Effects of Curcumin on Cellular Concentration and Pharmacokinetics of Gemcitabine

Hongtao Xu et al.

Summary: Co-delivery of curcumin with gemcitabine using PSL not only increased the intracellular gemcitabine concentration and cytotoxicity to MIA PaCa-2 cells, but also significantly improved the pharmacokinetic profiles for both drugs.

PHARMACEUTICAL RESEARCH (2021)

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Article Multidisciplinary Sciences

Cytoplasmic RRM1 activation as an acute response to gemcitabine treatment is involved in drug resistance of pancreatic cancer cells

Tomotaka Kato et al.

Summary: High RRM1 expression in pancreatic cancer patients is associated with poorer clinical outcomes, especially in those receiving adjuvant chemotherapy. Activation of cytoplasmic RRM1 is related to cancer cell viability and drug resistance, while inhibition of RRM1 enhances the cytotoxic effects of gemcitabine for pancreatic cancer cells.

PLOS ONE (2021)

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Review Cell Biology

The metabolic flexibility of quiescent CSC: implications for chemotherapy resistance

Kangchen Chen et al.

Summary: Stem cells, including in adults and cancer, exhibit quiescence which can aid cancer stem cells in escaping chemotherapy. The tumor microenvironment provides signals to maintain stem cells in a quiescent state, making targeting TME components a potential treatment for chemotherapy resistance. Modulating metabolic pathways also shows promise in targeting stem cells and TME to limit resistance to chemotherapy.

CELL DEATH & DISEASE (2021)

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Article Multidisciplinary Sciences

The Atr-Chek1 pathway inhibits axon regeneration in response to Piezo-dependent mechanosensation

Feng Li et al.

Summary: The Atr-Chek1 pathway, involved in cell cycle and DNA damage response, inhibits axon regeneration in response to Piezo-mediated mechanosensation, affecting functional recovery. Targeting this pathway could potentially be useful for treating nervous system trauma.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

The inhibition of ABCB1/MDR1 or ABCG2/BCRP enables doxorubicin to eliminate liver cancer stem cells

Wang Yin et al.

Summary: Inhibiting MDR1 or ABCG2 was found to increase the sensitivity of liver cancer stem cells to doxorubicin, leading to elevated intracellular concentration of the drug and increased apoptosis. This approach effectively reversed chemoresistance in liver cancer stem cells, demonstrating a promising strategy for enhancing the therapeutic efficacy of doxorubicin.

SCIENTIFIC REPORTS (2021)

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Article Biochemistry & Molecular Biology

Genome instability and pressure on non-homologous end joining drives chemotherapy resistance via a DNA repair crisis switch in triple negative breast cancer

Adrian P. Wiegmans et al.

Summary: Chemotherapy is commonly used for cancers with high levels of inherent genome instability, but may lead to chemotherapy resistance due to dysregulation of DNA repair pathways. This study revealed that genome instability in triple negative breast cancer can cause dysregulation of the non-homologous end joining pathway, leading to the emergence of chemotherapy resistance.

NAR CANCER (2021)

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Article Gastroenterology & Hepatology

ZIP4 Increases Expression of Transcription Factor ZEB1 to Promote Integrin α3β1 Signaling and Inhibit Expression of the Gemcitabine Transporter ENT1 in Pancreatic Cancer Cells

Mingyang Liu et al.

GASTROENTEROLOGY (2020)

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Review Cell Biology

p53, cancer and the immune response

Julianne Blagih et al.

JOURNAL OF CELL SCIENCE (2020)

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Review Cell Biology

Role of JAK/STAT3 Signaling in the Regulation of Metastasis, the Transition of Cancer Stem Cells, and Chemoresistance of Cancer by Epithelial-Mesenchymal Transition

Wook Jin

CELLS (2020)

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Review Biochemistry & Molecular Biology

Mutant p53-Associated Molecular Mechanisms of ROS Regulation in Cancer Cells

Marco Cordani et al.

BIOMOLECULES (2020)

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Article Biochemistry & Molecular Biology

CD147 promotes DNA damage response and gemcitabine resistance via targeting ATM/ATR/p53 and affects prognosis in pancreatic cancer

Yinghui Zhou et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2020)

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Article Pharmacology & Pharmacy

The anti-DKK1 antibody DKN-01 as an immunomodulatory combination partner for the treatment of cancer

Jaclyn A. Wall et al.

EXPERT OPINION ON INVESTIGATIONAL DRUGS (2020)

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Article Cell Biology

Alpha Radiation as a Way to Target Heterochromatic and Gamma Radiation-Exposed Breast Cancer Cells

Maja Svetlicic et al.

CELLS (2020)

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Article Biochemistry & Molecular Biology

SphK2 confers 5-fluorouracil resistance to colorectal cancer via upregulating H3K56ac-mediated DPD expression

Yu-Hang Zhang et al.

ONCOGENE (2020)

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Article Multidisciplinary Sciences

A computational guided, functional validation of a novel therapeutic antibody proposes Notch signaling as a clinical relevant and druggable target in glioma

Dayana Herrera-Rios et al.

SCIENTIFIC REPORTS (2020)

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Review Cell & Tissue Engineering

Stem cell quiescence and its clinical relevance

Meng Luo et al.

WORLD JOURNAL OF STEM CELLS (2020)

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Review Oncology

Mutant p53 in Cancer Progression and Targeted Therapies

Gaoyang Zhu et al.

FRONTIERS IN ONCOLOGY (2020)

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Review Medicine, Research & Experimental

NOTCH4 maintains quiescent mesenchymal-like breast cancer stem cells via transcriptionally activating SLUG and GAS1 in triple-negative breast cancer

Lei Zhou et al.

THERANOSTICS (2020)

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Review Biochemistry & Molecular Biology

ABC Transporters: Regulation and Association with Multidrug Resistance in Hepatocellular Carcinoma and Colorectal Carcinoma

Maria Paula Ceballos et al.

CURRENT MEDICINAL CHEMISTRY (2019)

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Article Biochemistry & Molecular Biology

Thymidylate synthase maintains the de-differentiated state of triple negative breast cancers

Aarif Siddiqui et al.

CELL DEATH AND DIFFERENTIATION (2019)

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Article Cell Biology

Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer

Christopher J. Halbrook et al.

CELL METABOLISM (2019)

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Article Biochemistry & Molecular Biology

EZH2 cooperates with gain-of-function p53 mutants to promote cancer growth and metastasis

Yu Zhao et al.

EMBO JOURNAL (2019)

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Article Biochemistry & Molecular Biology

Cisplatin resistance involves a metabolic reprogramming through ROS and PGC-1α in NSCLC which can be overcome by OXPHOS inhibition

Alberto Cruz-Bermudez et al.

FREE RADICAL BIOLOGY AND MEDICINE (2019)

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Article Oncology

ROS/KRAS/AMPK Signaling Contributes to Gemcitabine-Induced Stem-like Cell Properties in Pancreatic Cancer

Hengqiang Zhao et al.

MOLECULAR THERAPY-ONCOLYTICS (2019)

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Article Cell Biology

H-Ferritin Affects Cisplatin-Induced Cytotoxicity in Ovarian Cancer Cells through the Modulation of ROS

Alessandro Salatino et al.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2019)

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Article Multidisciplinary Sciences

Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting

Pablo Hernandez-Camarero et al.

SCIENTIFIC REPORTS (2019)

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Review Biochemistry & Molecular Biology

Redox-Mediated Mechanism of Chemoresistance in Cancer Cells

Eun-Kyung Kim et al.

ANTIOXIDANTS (2019)

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Review Cell Biology

Understanding of ROS-Inducing Strategy in Anticancer Therapy

Su Ji Kim et al.

OXIDATIVE MEDICINE AND CELLULAR LONGEVITY (2019)

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Article Oncology

Role of Damage DNA-Binding Protein 1 in Pancreatic Cancer Progression and Chemoresistance

Yiyin Zhang et al.

CANCERS (2019)

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Article Oncology

Adipocytes promote breast cancer resistance to chemotherapy, a process amplified by obesity: role of the major vault protein(MVP)

Camille Lehuede et al.

BREAST CANCER RESEARCH (2019)

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Article Cell Biology

JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance

Tianyi Wang et al.

CELL METABOLISM (2018)

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Review Oncology

Revisiting the dynamic cancer stem cell model: Importance of tumour edges

Pablo Hernandez-Camarero et al.

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY (2018)

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Article Oncology

Mutant p53 blocks SESN1/AMPK/PGC-1 alpha/UCP2 axis increasing mitochondrial O-2-center dot production in cancer cells

Marco Cordani et al.

BRITISH JOURNAL OF CANCER (2018)

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Review Oncology

The role of cellular reactive oxygen species in cancer chemotherapy

Haotian Yang et al.

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2018)

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Article Oncology

Synergistic Effects of NOTCH/γ-Secretase Inhibition and Standard of Care Treatment Modalities in Non-small Cell Lung Cancer Cells

Venus Sosa Iglesias et al.

FRONTIERS IN ONCOLOGY (2018)

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Article Oncology

Gamma Secretase Inhibition by BMS-906024 Enhances Efficacy of Paclitaxel in Lung Adenocarcinoma

Katherine M. Morgan et al.

MOLECULAR CANCER THERAPEUTICS (2017)

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Article Multidisciplinary Sciences

Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine

Leore T. Geller et al.

SCIENCE (2017)

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Article Oncology

Posttranscriptional Upregulation of IDH1 by HuR Establishes a Powerful Survival Phenotype in Pancreatic Cancer Cells

Mahsa Zarei et al.

CANCER RESEARCH (2017)

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Article Biochemistry & Molecular Biology

DNA damage-induced ephrin-B2 reverse signaling promotes chemoresistance and drives EMT in colorectal carcinoma harboring mutant p53

S. K. Alam et al.

CELL DEATH AND DIFFERENTIATION (2016)

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Review Oncology

Cancer drug resistance: redox resetting renders a way

Yuan Liu et al.

ONCOTARGET (2016)

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Article Oncology

Acquired resistance to gemcitabine and cross-resistance in human pancreatic cancer clones

Hiroshi Yoneyama et al.

ANTI-CANCER DRUGS (2015)

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Article Oncology

Targeting CD133high Colorectal Cancer Cells In Vitro and In Vivo With an Asymmetric Bispecific Antibody

Lei Zhao et al.

JOURNAL OF IMMUNOTHERAPY (2015)

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Review Oncology

Revisiting STAT3 signalling in cancer: new and unexpected biological functions

Hua Yu et al.

NATURE REVIEWS CANCER (2014)

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Article Biochemistry & Molecular Biology

MicroRNA-128-2 targets the transcriptional repressor E2F5 enhancing mutant p53 gain of function

S. Donzelli et al.

CELL DEATH AND DIFFERENTIATION (2012)

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Review Biochemistry & Molecular Biology

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

L. Galluzzi et al.

CELL DEATH AND DIFFERENTIATION (2012)

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Article Pharmacology & Pharmacy

Multidrug Efflux Pumps and Cancer Stem Cells: Insights Into Multidrug Resistance and Therapeutic Development

K. Moitra et al.

CLINICAL PHARMACOLOGY & THERAPEUTICS (2011)

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Review Cell Biology

Signal transduction by reactive oxygen species

Toren Finkel

JOURNAL OF CELL BIOLOGY (2011)

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Article Biotechnology & Applied Microbiology

ChIP-on-Chip Analysis of In Vivo Mutant p53 Binding To Selected Gene Promoters

Stefania Dell'Orso et al.

OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY (2011)

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Review Cell Biology

The impact of acetylation and deacetylation on the p53 pathway

Christopher L. Brooks et al.

PROTEIN & CELL (2011)

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Review Biochemistry & Molecular Biology

Cisplatin resistance: Preclinical findings and clinical implications

Beate Koeberle et al.

BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2010)

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Review Biochemistry & Molecular Biology

Oxidative stress, inflammation, and cancer How are they linked?

Simone Reuter et al.

FREE RADICAL BIOLOGY AND MEDICINE (2010)

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Review Biochemistry & Molecular Biology

Activation of the hedgehog-signaling pathway in human cancer and the clinical implications

L. Yang et al.

ONCOGENE (2010)

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Review Biochemistry & Molecular Biology

p53 alterations in human cancer: more questions than answers

T. Soussi

ONCOGENE (2007)

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Article Oncology

Gemcitabine chemoresistance and molecular markers associated with gemcitabine transport and metabolism in human pancreatic cancer cells

Y. Nakano et al.

BRITISH JOURNAL OF CANCER (2007)

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Article Biochemistry & Molecular Biology

Mutant p53 gain of function: reduction of tumor malignancy of human cancer cell lines through abrogation of mutant p53 expression

G Bossi et al.

ONCOGENE (2006)

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Article Biochemistry & Molecular Biology

Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome

GA Lang et al.

CELL (2004)

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Review Urology & Nephrology

The p53 tumor suppressor gene and nuclear protein: Basic science review and relevance in the management of bladder cancer

ND Smith et al.

JOURNAL OF UROLOGY (2003)

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Article Biochemistry & Molecular Biology

Mutant p53 cooperates with ETS and selectively up-regulates human MDR1 not MRP1

J Sampath et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2001)

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Article Oncology

Mixture of trypsin, chymotrypsin and papain reduces formation of metastases and extends survival time of C57Bl6 mice with syngeneic melanoma B16

M Wald et al.

CANCER CHEMOTHERAPY AND PHARMACOLOGY (2001)

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