Introduction to Cancer Resistant

What is/are Cancer Resistant?

Cancer Resistant - The naked mole rat (nmr) is cancer resistant due to the abundant production of extremely high-molecular-weight hyaluronan (EHMW-HA). ^[1] Interestingly, in wild animals, p53 variations contribute to cancer resistant and high longevity. ^[2]

anaplastic lymphoma kinase

Genetic rearrangements of anaplastic lymphoma kinase contribute to the pathogenesis of non‐small‐cell lung cancer; the anaplastic lymphoma kinase inhibitor, ceritinib, is widely used, as it is effective even in patients with non‐small‐cell lung cancer resistant to other anaplastic lymphoma kinase inhibitors. ^[1]

Breast Cancer Resistant

1014 Background: The randomized PEARL trial found no superiority of palbociclib plus endocrine therapy over capecitabine in patients (pts) with metastatic HR-positive, HER2-negative breast cancer resistant to prior aromatase inhibitors (Martin M, Ann Oncol 2020). ^[1] A common mechanism for MDR is the overexpression of an active ATP-binding cassette (ABC) transporter protein: either the P-glycoprotein (P-gp/ABCB1, also known as MDR1), the multidrug resistance protein 1 (MRP1/ABCC1) or the breast cancer resistant protein (BCRP/ABCG2), on the plasma membrane of cancer cells. ^[2] Both neuroscience and non-neuroscience therapeutic areas have struggled to quantitatively estimate brain penetration or the lack thereof with compounds that are substrates of efflux transport proteins such as P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) that are key components of the blood-brain barrier (BBB). ^[3] Finally, we found high CDK2 levels in cells resistant to combined fulvestrant and PI3Ki, and targeting ER, PI3K, and CDK2 offered an additional treatment option for ER+ breast cancer resistant to combined fulvestrant and PI3Ki. ^[4] Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. ^[5] Indeed, EVs isolated from tumor and stromal cells act as key messengers in intercellular communications able to propagate traits of resistance and/or educate the microenvironment to sustain a breast cancer resistant phenotype. ^[6] The studies on their therapeutic effects on human breast cancer resistant cells verified the feasibility of the modular approach, indicated that the two modular targeted drug delivery systems: 1) retain the drug toxicity and cell-killing effect of the prodrug module, 2) have precise targeting capabilities due to mitochondrial targeting module, 3) enhance drug uptake, reduce drug efflux and reverse the multidrug resistance (MDR) effect to a certain extent. ^[7] The present study evaluates poly (butyl cyanoacrylate) nanoparticles (PBCA-NPs), double-coated with Tween 80 and polyethylene glycol (PEG) 20,000 as a potential carrier system for overcoming P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)-mediated multidrug resistance (MDR) in cancer cell lines. ^[8] BACKGROUND The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. ^[9] Combined with trastuzumab or tamoxifen, M2698 demonstrated antitumor activity in patients with advanced breast cancer resistant to multiple standard therapies, suggesting that it could overcome treatment resistance. ^[10] Furthermore, they also provide direct evidence validating that the above strategy does restrain cancer progression in a mouse model of breast cancer resistant to immune-checkpoint or anti-VEGF therapies. ^[11] Moreover, both GCV and compound 1 were found to interact with breast cancer resistant protein (BCRP) more effectively than multidrug-resistant proteins (MRPs) in these cells. ^[12] STUDY DESIGN Multiple modelling strategies were applied with three main mottos: (a) Generation of robust classification models to identify the linear and non-linear relationships among the natural compounds and the inhibition of BCRP, (b) Identification of important structural fingerprints that modulate BCRP inhibition and screening of natural database to find the probable hit molecules, (c) Comprehensive ligand-receptor interactions analysis of those against the putative breast cancer resistant protein through molecular docking analysis. ^[13] In the present study, we revealed that the expression of CK18 was significantly downregulated in breast cancer tissues and in an MDR cell line overexpressing breast cancer resistant protein (BCRP), and the presence of low levels of CK18 was associated with TNM stage, lymph node metastasis, and unfavorable survival in breast cancer patients. ^[14] BACKGROUND Recent US Food and Drug Administration (FDA) draft guidance on pharmacokinetic drugdrug interactions (DDIs) has highlighted the clinical importance of ABC transporters B1 or P-glycoprotein (P-gp), hepatic organic anion-transporting polypeptide transporters and breast cancer resistant protein because of their broad substrate specificity and the potential to be involved in DDIs. ^[15] The purpose of this review is to summarize unique characteristics of human breast cancer resistant protein (BCRP) and the genetic variability in the BCRP encoded gene ABCG2 in the development of precision medicine. ^[16] In the ACe trial, postmenopausal women with HR+HeR2– advanced-stage breast cancer resistant to endocrine therapy were randomly assigned to receive the aromatase inhibitor exemestane together with tucidinostat (n = 244) or placebo (n = 121). ^[17] To characterize the signaling events that govern EGFR behavior in metastatic breast cancer resistant to EGFRi, we utilized multiple pre-clinical breast cancer progression series and patient-derived cells that display the intrinsic resistance phenomenon. ^[18] RNAseq analysis confirmed the expression of key BBB-related genes in the hiPSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells, including P-glycoprotein (Pgp) and breast cancer resistant protein (BCRP). ^[19] The functional expression of two efflux transporters P-glycoprotein (P-gp) and Breast Cancer Resistant Protein (BCRP) was shown to be negligible by bidirectional transport studies using appropriate transporter substrates and inhibitors. ^[20] The ability of the nanoparticle to overcome multi-drug resistance was evaluated by the expression of multidrug-resistant proteins P-glycoprotein (P-gp) and Breast cancer resistant protein (BCRP) in lung adenocarcinoma resistant cells (A549R). ^[21] Furthermore, expressions of CXCR4 and CCR5 were found to be associated with poor prognosis in this cohort with triple negative breast cancer resistant to chemotherapy that would justify an addititional chemokine receptor inhibitor therapy. ^[22] The brain uptake was increased in a P-glycoprotein and breast cancer resistant protein double knockout mouse, when compared to a wild-type mouse. ^[23] Abbreviations: HCC: Hepatocellular Carcinoma; FDA: Food and Drug Administration; TGF-β: Transforming growth factor-β; PXR: Pregnane X receptor; CAR: Constitutive androstane receptor; P-gp/ABCB1: P-glycoproteins/ATP-binding cassette transporter subfamily B member 1; MRP1/ABCC1 and MRP2/ABCC2: Multidrug-resistance associated proteins; BCRP/ABCG2: Breast cancer resistant protein; DMEs: Drug-metabolizing enzymes; CFDA: 5,6-carboxyfluorescein diacetate; ETS1: Transcription factor E26 transformation specific sequence 1. ^[24] Methods The MCF-7/ADM1 and MCF-7/ADM2 of breast cancer resistant cell lines were induced by low-concentration continuous increasing method and high concentration impact increasing method respectively. ^[25] Second, this panel was applied to characterize uncultured and cultured CTCs, which were enriched from a cryopreserved DLA product obtained from a patient suffering from metastatic breast cancer resistant to endocrine therapy. ^[26] Therefore, cardamonin may serve as a therapeutic agent for patients with cervical and breast cancer resistant to mTOR inhibitors. ^[27] One crucial limitation in the pharmacotherapy for this tumour is its chemotherapy‐resistant nature produced by the overexpression of several members of the ATP‐binding cassette protein family that efflux drugs out of cells, as observed with the breast cancer resistant protein (BCRP). ^[28] However, in large retrospective studies, ESR1 mutations occurred in up to 39% of Estrogen-Receptor(ER)-positive metastatic breast cancer resistant to AI. ^[29] Here we describe a clinical case of patient with heavily pretreated metastatic triple negative breast cancer resistant to taxanes, anthracyclines and eribuline who was successfully treated with ixabepilone and capecitabine combination. ^[30] Using a confocal based assay, we measured the ex vivo and in vivo effects of TBBPA on P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) transport activity in rat brain capillaries. ^[31] The aim of this study was to examine the effect of ER on the quantitative predictivity of brain disposition toward compounds with MDR1 and/or breast cancer resistant protein (BCRP) liabilities. ^[32]

Prostate Cancer Resistant

Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. ^[1] Background: The therapeutic standard for oligoprogressive prostate cancer resistant to castration is second-generation hormone therapy. ^[2] Patient summary We measured blood levels of testosterone and other male hormones before treatment with enzalutamide among men with prostate cancer resistant to castration. ^[3] Patient summary Treatment with a radioactive binding molecule called [177Lu]-PSMA-617 for men with prostate cancer resistant to castration (CRPC) is showing promise. ^[4] Materials and methods: From January 2011 to December 2016, all medical records of patients with a diagnosis of prostate cancer resistant to the effects of castration presenting at Shaukat Khanum Cancer Hospital and Research Centre, Lahore, were reviewed. ^[5]

Lung Cancer Resistant

These effects suggesting that CAF can be a therapeutic target in lung cancer resistant to checkpoint inhibitors. ^[1] Therefore, this pathway can be exploited in patients with lung cancer resistant to targeted therapies. ^[2] Genetic rearrangements of anaplastic lymphoma kinase contribute to the pathogenesis of non‐small‐cell lung cancer; the anaplastic lymphoma kinase inhibitor, ceritinib, is widely used, as it is effective even in patients with non‐small‐cell lung cancer resistant to other anaplastic lymphoma kinase inhibitors. ^[3] Here, we perform a systems analysis of a model of EGFR‐mutated nonsmall cell lung cancer resistant to targeted therapy that integrates whole exome sequencing, global time‐course discovery phosphoproteomics and computational modeling to identify functionally relevant molecular alterations. ^[4]

Colorectal Cancer Resistant

In the setting of colorectal cancer resistant to conventional chemotherapy, Hepatic Arterial infusion (HAI) using floxuridine yielded high response rates in multithreaded patients (4). ^[1] Results In this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and non-resistant cells. ^[2] GC1118 showed promising antitumor activity, especially in patients with colorectal cancer resistant to prior EGFR antibody. ^[3]

Lethal Cancer Resistant

Pancreatic ductal adenocarcinoma (PDA) is a lethal cancer resistant to immunotherapy. ^[1] Malignant glioma (glioblastoma, GBM) is a lethal cancer resistant to multimodality therapeutic approaches. ^[2]

cancer resistant protein

A common mechanism for MDR is the overexpression of an active ATP-binding cassette (ABC) transporter protein: either the P-glycoprotein (P-gp/ABCB1, also known as MDR1), the multidrug resistance protein 1 (MRP1/ABCC1) or the breast cancer resistant protein (BCRP/ABCG2), on the plasma membrane of cancer cells. ^[1] Both neuroscience and non-neuroscience therapeutic areas have struggled to quantitatively estimate brain penetration or the lack thereof with compounds that are substrates of efflux transport proteins such as P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP) that are key components of the blood-brain barrier (BBB). ^[2] Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. ^[3] The present study evaluates poly (butyl cyanoacrylate) nanoparticles (PBCA-NPs), double-coated with Tween 80 and polyethylene glycol (PEG) 20,000 as a potential carrier system for overcoming P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)-mediated multidrug resistance (MDR) in cancer cell lines. ^[4] Moreover, both GCV and compound 1 were found to interact with breast cancer resistant protein (BCRP) more effectively than multidrug-resistant proteins (MRPs) in these cells. ^[5] STUDY DESIGN Multiple modelling strategies were applied with three main mottos: (a) Generation of robust classification models to identify the linear and non-linear relationships among the natural compounds and the inhibition of BCRP, (b) Identification of important structural fingerprints that modulate BCRP inhibition and screening of natural database to find the probable hit molecules, (c) Comprehensive ligand-receptor interactions analysis of those against the putative breast cancer resistant protein through molecular docking analysis. ^[6] In the present study, we revealed that the expression of CK18 was significantly downregulated in breast cancer tissues and in an MDR cell line overexpressing breast cancer resistant protein (BCRP), and the presence of low levels of CK18 was associated with TNM stage, lymph node metastasis, and unfavorable survival in breast cancer patients. ^[7] BACKGROUND Recent US Food and Drug Administration (FDA) draft guidance on pharmacokinetic drugdrug interactions (DDIs) has highlighted the clinical importance of ABC transporters B1 or P-glycoprotein (P-gp), hepatic organic anion-transporting polypeptide transporters and breast cancer resistant protein because of their broad substrate specificity and the potential to be involved in DDIs. ^[8] The purpose of this review is to summarize unique characteristics of human breast cancer resistant protein (BCRP) and the genetic variability in the BCRP encoded gene ABCG2 in the development of precision medicine. ^[9] RNAseq analysis confirmed the expression of key BBB-related genes in the hiPSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells, including P-glycoprotein (Pgp) and breast cancer resistant protein (BCRP). ^[10] The functional expression of two efflux transporters P-glycoprotein (P-gp) and Breast Cancer Resistant Protein (BCRP) was shown to be negligible by bidirectional transport studies using appropriate transporter substrates and inhibitors. ^[11] The ability of the nanoparticle to overcome multi-drug resistance was evaluated by the expression of multidrug-resistant proteins P-glycoprotein (P-gp) and Breast cancer resistant protein (BCRP) in lung adenocarcinoma resistant cells (A549R). ^[12] The brain uptake was increased in a P-glycoprotein and breast cancer resistant protein double knockout mouse, when compared to a wild-type mouse. ^[13] Abbreviations: HCC: Hepatocellular Carcinoma; FDA: Food and Drug Administration; TGF-β: Transforming growth factor-β; PXR: Pregnane X receptor; CAR: Constitutive androstane receptor; P-gp/ABCB1: P-glycoproteins/ATP-binding cassette transporter subfamily B member 1; MRP1/ABCC1 and MRP2/ABCC2: Multidrug-resistance associated proteins; BCRP/ABCG2: Breast cancer resistant protein; DMEs: Drug-metabolizing enzymes; CFDA: 5,6-carboxyfluorescein diacetate; ETS1: Transcription factor E26 transformation specific sequence 1. ^[14] One crucial limitation in the pharmacotherapy for this tumour is its chemotherapy‐resistant nature produced by the overexpression of several members of the ATP‐binding cassette protein family that efflux drugs out of cells, as observed with the breast cancer resistant protein (BCRP). ^[15] Using a confocal based assay, we measured the ex vivo and in vivo effects of TBBPA on P-glycoprotein (P-gp), breast cancer resistant protein (BCRP), and multidrug resistance-associated protein 2 (MRP2) transport activity in rat brain capillaries. ^[16] The aim of this study was to examine the effect of ER on the quantitative predictivity of brain disposition toward compounds with MDR1 and/or breast cancer resistant protein (BCRP) liabilities. ^[17]

cancer resistant cell

Current treatments including chemotherapy can induce cell death only in bulk cancer cells sparing CSCs and cancer resistant cells (CRCs) which are shown to be responsible for high recurrence of disease and low patient survival. ^[1] The studies on their therapeutic effects on human breast cancer resistant cells verified the feasibility of the modular approach, indicated that the two modular targeted drug delivery systems: 1) retain the drug toxicity and cell-killing effect of the prodrug module, 2) have precise targeting capabilities due to mitochondrial targeting module, 3) enhance drug uptake, reduce drug efflux and reverse the multidrug resistance (MDR) effect to a certain extent. ^[2] Current treatments including chemotherapy can induce cell death only in bulk cancer cells sparing CSCs and cancer resistant cells (CRCs) which are shown to be responsible for high recurrence of disease and low patient survival. ^[3] The expression of linc00161, miR‐128 and MAPK1 in ovarian cancer‐resistant tissues and cells was tested qRT‐PCR, whereas MAPK1 protein expression was examined via western blot in the ovarian cancer resistant cells. ^[4] Methods The MCF-7/ADM1 and MCF-7/ADM2 of breast cancer resistant cell lines were induced by low-concentration continuous increasing method and high concentration impact increasing method respectively. ^[5] Current treatments including chemotherapy can induce cell death only in bulk cancer cells sparing CSCs and cancer resistant cells (CRCs) which are shown to be responsible for high recurrence of disease and low patient survival. ^[6]