• binds
  • Ramucirumab (marketed under the brand name CYRAMZA®) is an immunoglobulin G1 VEGFR-2 monoclonal antibody that binds to the extracellular domain of VEGFR-2 with high specificity and affinity, competing with VEGF-A, -C, and -D. CYRAMZA (ramucirumab) is approved for use in certain patients with previously treated advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, non-small-cell lung cancer (NSCLC), and colorectal cancer. (phacilitate.co.uk)
  • The active site, at residues 181, 200, 97, and 85, binds the terminal phosphate of ATP and transfers it to the target location on the substrate (see figure 1). (wikipedia.org)
  • Activated TGF-β complexes with other factors to form a serine/threonine kinase complex that binds to TGF-β receptors, which is composed of both type 1 and type 2 receptor subunits. (wikipedia.org)
  • Most kinases are inhibited by a pseudosubstrate that binds to the kinase like a real substrate but lacks the amino acid to be phosphorylated. (wikipedia.org)
  • ACTH binds to the MC2 receptor in the Zona fasciculata of the adrenal cortex, and stimulates secretion of the stress hormone cortisol. (wikipedia.org)
  • Anaplastic Lympho
  • The U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to Keytruda (pembrolizumab) for the treatment of patients with Epidermal Growth Factor Receptor (EGFR) mutation-negative, and Anaplastic Lymphoma Kinase (ALK) rearrangement-negative non-small cell lung cancer (NSCLC) whose disease has progressed on or following platinum-based chemotherapy. (drugs.com)
  • The following is the list of known dependence receptors: Notch3 Kremen1 DCC (Deleted in Colorectal Carcinoma) UNC5 receptors (UNC5A, UNC5B, UNC5C, UNC5D) Neogenin p75NTR Ptch1 CDON PLXND1 RET TrkA TrkC EphA4 c-Met Insulin Receptor IR Insulin-like growth factor 1 receptor ALK (Anaplastic Lymphoma Kinase) Androgen Receptor Some integrins NTRK3 Cells depend for their survival on stimulation that is mediated by various receptors and sensors. (wikipedia.org)
  • inhibition
  • In cellular migration, an integral aspect of inflammatory responses, the inhibition of GSK-3 has been reported to play conflicting roles, as local inhibition at growth cones has been shown to promote motility while global inhibition of cellular GSK-3 has been shown to inhibit cell spreading and migration. (wikipedia.org)
  • AUSTIN, TX, USA I April 2, 2017 I Genprex, Inc. announced new pre-clinical data which reveal that TUSC2 (formerly known as FUS1, the active anti-cancer agent in Oncoprex TM ) in combination with PD-1 checkpoint inhibition has a significantly greater anti-tumor effect in lung cancer than either agent alone. (pipelinereview.com)
  • Various dependence receptors are involved in a range of biological events: developmental cell death (naturally occurring cell death), trophic factor withdrawal-induced cell death, the spontaneous regression characteristic of type IV-S neuroblastoma, neurodegenerative cell death, inhibition of new tumor cells (tumorigenesis) and metastasis, and therapeutic antibody-mediated tumor cell death, as well as programmed cell death in other instances. (wikipedia.org)
  • Suppression of inflammation involves both direct inhibition of pro-inflammatory cytokine production and release of anti-inflammatory factors, which all contribute to the resolution of inflammation. (pubmedcentralcanada.ca)
  • Attempts at treatment for cancer cells with constitutively phosphorylated STAT5 have included both indirect and direct inhibition of STAT5 activity. (wikipedia.org)
  • While more medicinal work has been done in indirect inhibition, this approach can lead to increased toxicity in cells and can also result in non-specific effects, both of which are better handled by direct inhibition. (wikipedia.org)
  • Indirect inhibition targets kinases associated with STAT5, or targets proteases that carry out terminal truncation of proteins. (wikipedia.org)
  • Different inhibitors have been designed to target different kinases: inhibition of BCR/ABl constitutes the basis of the functioning of drugs like imatinib inhibition of FLT3 is carried out by drugs like lestaurtinib inhibition of JAK2 is carried out by the drug CYT387, which was successful in preclinical trials and is currently undergoing clinical trials. (wikipedia.org)
  • Proteins
  • The connections between Sirt 1 and other anti-aging genes such as Klotho, p66Shc (longevity protein) and Forkhead box proteins (FOXO1/ FOXO3a) have been associated with programmed cell death and alterations in these anti-aging genesregulate glucose, lipid and amyloid beta metabolism that are important to various chronic diseases. (scirp.org)
  • Transforming growth factor beta (TGF-β) is a multifunctional cytokine belonging to the transforming growth factor superfamily that includes four different isoforms (TGF-β 1 to 4, HGNC symbols TGFB1, TGFB2, TGFB3, TGFB4) and many other signaling proteins produced by all white blood cell lineages. (wikipedia.org)
  • The region between the fifth and sixth conserved cysteines houses the most divergent area of TGF-β proteins that is exposed at the surface of the protein and is implicated in receptor binding and specificity of TGF-β. (wikipedia.org)
  • In cellular biology, dependence receptors are proteins that mediate programmed cell death by monitoring the absence of certain trophic factors (or, equivalently, the presence of anti-trophic factors) that otherwise serve as ligands (interactors) for the dependence receptors. (wikipedia.org)
  • Thus cells that express these proteins at sufficient concentrations manifest a state of dependence on their respective ligands. (wikipedia.org)
  • MSC can be modified to carry therapeutic genes, serving as programmed molecule transmitters to overcome limitations connected with direct injection of beneficial proteins. (biomedcentral.com)
  • Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. (wikipedia.org)
  • These recruited proteins are then responsible for the subsequent activation of other downstream proteins, including protein kinases (IKKi, IRAK1, IRAK4, and TBK1) that further amplify the signal and ultimately lead to the upregulation or suppression of genes that orchestrate inflammatory responses and other transcriptional events. (wikipedia.org)
  • A third subgroup of proteins containing TIR domains consists of adaptor proteins that are exclusively cytosolic and mediate signaling from proteins of subgroups 1 and 2. (wikipedia.org)
  • These interactions allow DLC1 to co-localize along with these proteins to focal adhesions at the periphery of the cell, where it is able to carry out its function as a Rho-GAP protein. (wikipedia.org)
  • This can occur with replication fork barriers, proteins such as PTIP, CHD4 and PARP1, which are normally cleared by the cell´s DNA damage sensors, surveyors, and responders BRCA1 and BRCA2. (wikipedia.org)
  • The reaction inactivates or reduces the activity of various functionally important target proteins and is one mechanism by which cylopentenone PGs influence cell function. (wikipedia.org)
  • Types include those acting directly as receptors (Receptor protein serine/threonine kinase) and Intracellular signaling peptides and proteins. (wikipedia.org)
  • Once ruptured, particles and substances are released, including: (1) high mobility group B-1 (HMGB1) (2) heat shock proteins and (3) various other proteases. (wikipedia.org)
  • NGF is initially in a 7S, 130-kDa complex of 3 proteins - Alpha-NGF, Beta-NGF, and Gamma-NGF (2:1:2 ratio) when expressed. (wikipedia.org)
  • phosphorylation
  • In addition to its role in regulating glycogen synthase, GSK-3 has been implicated in other aspects of glucose homeostasis, including the phosphorylation of insulin receptor IRS1 and of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6 phosphatase. (wikipedia.org)
  • We investigated PPP's activity in panels of human cancer cell lines (e.g., esophageal squamous carcinoma cell lines) but found no effects on the phosphorylation or expression of IGF-IR. (aacrjournals.org)
  • metastasis
  • The study, conducted by Jack A. Roth, M.D., F.A.C.S., and his team at The University of Texas MD Anderson Cancer Center in Houston, evaluated the immune response of TUSC2 alone and in combination with anti-PD-1 agents across five independent experiments in two syngeneic mouse models, including a model of lung metastasis. (pipelinereview.com)
  • TUSC2 alone or in combination with checkpoint blockade (anti-PD-1 and/or anti-CTLA4) significantly prolonged mouse survival in the NSCLC metastasis model compared to checkpoint blockade alone. (pipelinereview.com)
  • This process is seen in developmental cell death, carcinogenesis (especially metastasis), neurodegeneration, and possibly non-lethal (sub-apoptotic) events such as neurite retraction and somal atrophy. (wikipedia.org)
  • ANGPTL4 disrupts endothelial cell junctions by directly interacting with integrin, VE-cadherin and claudin-5 in a sequential manner to facilitate metastasis. (wikipedia.org)
  • serine or threonine
  • While serine/threonine kinases all phosphorylate serine or threonine residues in their substrates, they select specific residues to phosphorylate on the basis of residues that flank the phosphoacceptor site, which together comprise the consensus sequence. (wikipedia.org)
  • vivo
  • This was evident as pronounced neutrophil migration upon exposure of macrophages to apoptotic cells in an in vivo peritonitis model. (pubmedcentralcanada.ca)
  • In vivo , apoptotic cells are usually engulfed by neighboring cells or professional phagocytes, such as macrophages ( 1 ). (pubmedcentralcanada.ca)
  • showed that anisomycin can sensitize metastatic epithelial cells to anoikis and reduce circulating tumor cell implantation in vivo. (wikipedia.org)
  • ANGPTL4 is also a potent angiogenic factor whose expression is up-regulated in hypoxic retinal Müller cells in vitro and the ischemic retina in vivo. (wikipedia.org)
  • residues
  • The death domain (DD) is a conserved region of about 80 residues found on death receptors, and which is required for death signalling, as well as a variety of non-apoptotic functions [ PMID: 11828422 , PMID: 12655292 ]. (ebi.ac.uk)
  • After being primed by casein kinase 2 (CK2), glycogen synthase gets phosphorylated at a cluster of three C-terminal serine residues, reducing its activity. (wikipedia.org)
  • Since the consensus sequence residues of a target substrate only make contact with several key amino acids within the catalytic cleft of the kinase (usually through hydrophobic forces and ionic bonds), a kinase is usually not specific to a single substrate, but instead can phosphorylate a whole "substrate family" which share common recognition sequences. (wikipedia.org)
  • genes
  • Interests in anti-aging therapy with appetite regulation improve an individual's survival to metabolic disease induced by gene-environment interactions by maintenance of the anti-aging genes connected to the metabolism of bacterial lipopolysaccharides, drugs and xenobiotics. (scirp.org)
  • In the aging process as the anti-aging genes are suppressed as a result of transcriptional dysregulation chronic disease accelerations and connected to insulin resistance, non-alcoholic fatty liver disease (NAFLD) and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. (scirp.org)
  • This constant activation is brought about either by mutations or by aberrant expressions of cell signalling, resulting in poor regulation, or complete lack of control, of the activation of transcription for genes influenced by STAT5. (wikipedia.org)
  • For example, mutations may lead to increased expression of anti-apoptotic genes, the products of which actively prevent cell death. (wikipedia.org)
  • While the catalytic domain of these kinases is highly conserved, the sequence variation that is observed in the kinome (the subset of genes in the genome that encode kinases) provides for recognition of distinct substrates. (wikipedia.org)
  • enzymes
  • While the phagocytosis of a variety of pathogenic targets, especially bacteria and virally-infected cells, normally triggers a pro-inflammatory response in macrophages (including the generation of reactive oxygen-derived intermediates, the release of proteolytic enzymes, and the production of numerous inflammatory cytokines), ingestion of apoptotic cells by macrophages usually induces an anti-inflammatory phenotype. (pubmedcentralcanada.ca)
  • stimuli
  • 1 ) attraction of phagocytes via soluble `find me' signals, ( 2 ) recognition and phagocytosis via cell surface presenting `eat me' signals, and ( 3 ) suppression or initiation of inflammatory responses depending on additional innate immune stimuli. (pubmedcentralcanada.ca)
  • Nevertheless, it is not known whether the Fas-receptor stimuli or the ASK1 overexpression are caused by ROS or CRM1 mediated export. (wikipedia.org)
  • This protein is involved in the programmed cell death induced by Fas and various apoptotic stimuli. (wikipedia.org)
  • induces
  • The data further support a direct effect of TUSC2 on various immune cells which induces a synergistic antitumor immune response. (pipelinereview.com)
  • In the process of inflammation, NGF is released in high concentrations by mast cells, and induces axonal outgrowth in nearby nociceptive neurons. (wikipedia.org)
  • novel
  • Consequently, these three cyclopentenone-PGs and the two epoxyisoprostanes are suggested to be models for the development of novel anti-inflammatory and anti-cancer drugs. (wikipedia.org)
  • metastatic
  • 1], This disease is serious and life-threatening, and approximately 20-30% of patients are first diagnosed at an advanced or metastatic stage. (perssupport.nl)
  • The FDA previously granted avelumab Breakthrough Therapy Designation for the treatment of patients with metastatic Merkel cell carcinoma (mMCC) whose disease has progressed after at least one previous chemotherapy regimen. (perssupport.nl)
  • DLC1 is also involved in the formation of focal adhesions, so loss of DLC1 leads to reduced cell adhesion and increased metastatic potential of cells. (wikipedia.org)
  • However, metastatic tumor cells may escape from anoikis and invade other organs. (wikipedia.org)
  • Anisomycin achieved this anti-metastatic activity in part by decreasing the abundance of the death receptor inhibiting protein FLIP. (wikipedia.org)
  • In related work, Schimmer's team showed that FLIP levels are higher in metastatic cells than non-metastatic cells, and that reducing FLIP levels using RNAi (RNA Interference) or other small molecule inhibitors of FLIP can sensitize metastatic cells to anoikis. (wikipedia.org)
  • ANGPTL4 plays an important role in numerous cancers and is implicated in the metastatic process by modulating vascular permeability, cancer cell motility and invasiveness. (wikipedia.org)
  • regulation
  • Therefore, in addition to transmitting mechanical forces across otherwise vulnerable membranes, they are involved in cell signaling and the regulation of cell cycle, shape, and motility. (hindawi.com)
  • It has been associated with heterochromatin and PML-NBs (Promyelocytic Leukaemia nuclear bodies) and has been implicated in many nuclear processes including transcription and cell cycle regulation. (wikipedia.org)
  • In cancer cells, where normal regulation of gene expression breaks down, the oncogenes are activated via hypomethylation and tumor suppressors are silenced via hypermethylation. (wikipedia.org)
  • Since it was first isolated by Nobel Laureates Rita Levi-Montalcini and Stanley Cohen in 1956, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system. (wikipedia.org)
  • specificity
  • The hybridoma technology developed in the mid-1970s by Köhler and Milstein ( 1 ) proved to be an efficient means to isolate single specificity antibodies and produce them in unlimited amounts. (frontiersin.org)
  • mediate
  • In the present study, using wild type and adenosine A 2A receptor (A2AR) null mice, we investigated whether A2ARs, known to mediate anti-inflammatory signals in macrophages, participate in the apoptotic cell-mediated immunosuppression. (pubmedcentralcanada.ca)
  • Altogether our data indicate that adenosine is one of the soluble mediators released by macrophages that mediate engulfment-dependent apoptotic cell suppression of inflammation. (pubmedcentralcanada.ca)
  • cytoplasmic
  • Daxx, a Death domain-associated protein, was first discovered through its cytoplasmic interaction with the classical death receptor Fas. (wikipedia.org)
  • At the level of the cell, Daxx is found in the cytoplasm, interacting with Fas-receptor or other cytoplasmic molecules, as well as in the nucleus, where it is interacting with some subnuclear structures. (wikipedia.org)
  • Terms such as "cytoplasmic" and "type 3 cell death" had previously been used to describe these forms of cell death. (wikipedia.org)
  • Instead, paraptosis displays a somewhat primitive cell death path, comparable to necrosis, including characteristic cytoplasmic vacuole formation and late mitochondrial swelling and clumping. (wikipedia.org)
  • Almost immediately, major structural rearrangements such as rounded cells, cytoplasmic reorganization, and vacuolation of cells undergoing paraptosis can be seen through light microscopy. (wikipedia.org)
  • inhibitors
  • Promising antitumor activity has been observed in multiple tumor types with anti-PD-1/PD-L1 immune checkpoint inhibitors. (phacilitate.co.uk)
  • These data suggest that TUSC2 could become a promising new treatment approach to lung cancer, particularly in combination with approved PD-1 checkpoint inhibitors, such as nivolumab," said Julien Pham, M.D., MPH, COO of Genprex. (pipelinereview.com)
  • undergo
  • As they become apoptotic, cells undergo dramatic changes in the composition of their surface, which allows their recognition by phagocytes and subsequent removal. (pubmedcentralcanada.ca)
  • When cells are detached from the ECM, there is a loss of normal cell-matrix interactions, and they may undergo anoikis. (wikipedia.org)
  • tumor cell death
  • Oncoprex is an optimized TUSC2 gene encapsulated in a fatty, positively charged nanovesicle (a nanoscale hollow sphere) injected intravenously, which can specifically target cancer cells and insert wild-type TUSC2 into cellular DNA, effectively increasing expression of the TUSC2 protein and promoting tumor cell death. (pipelinereview.com)
  • peroxisome
  • We found that macrophages engulfing apoptotic cells release adenosine in sufficient amount to trigger A2ARs, and simultaneously increase the expression of A2ARs, possibly via activation of activation of liver X receptor and peroxisome proliferators activated receptor δ. (pubmedcentralcanada.ca)
  • This gene is induced under hypoxic (low oxygen) condition in various cell types and is the target of Peroxisome proliferator-activated receptors. (wikipedia.org)
  • Molecular
  • This was achieved through bioactivity guided fractionation, theoretical molecular docking, and functional enzyme studies, followed by in vitro evaluation in a human breast cancer cell line with dominant protein expression of h LDH-A. (hindawi.com)
  • TLRs are a type of pattern recognition receptor (PRR) and recognize molecules that are broadly shared by pathogens but distinguishable from host molecules, collectively referred to as pathogen-associated molecular patterns (PAMPs). (wikipedia.org)
  • Molecular building blocks of the TLRs are represented in bacteria and in plants, and plant pattern recognition receptors are well known to be required for host defence against infection. (wikipedia.org)
  • BAG family molecular chaperone regulator 1 is a protein that in humans is encoded by the BAG1 gene. (wikipedia.org)
  • 1993
  • Dependence receptors were first identified in 1993 in the laboratory of Dale Bredesen, and their importance in tumorigenesis first described by Mehlen, Bredesen, and their colleagues. (wikipedia.org)
  • Hamster cell research in 1993 showed that amplifications in the DHFR gene involved in DNA synthesis began with chromosome break in below the gene, and subsequent cycles of bridge-breakage-fusion formations result in large intrachromosomal repeats. (wikipedia.org)
  • imatinib
  • On 1 February 2012, imatinib was approved for use after the surgical removal of KIT-positive tumors to help prevent recurrence. (wikipedia.org)
  • Imatinib is specific for the TK domain in abl (the Abelson proto-oncogene), c-kit and PDGF-R (platelet-derived growth factor receptor). (wikipedia.org)
  • Inflammation
  • Apoptotic cell clearance is believed to represent a critical process in tissue remodeling, maintenance of immune homeostasis, and resolution of inflammation ( 2 , 3 ). (pubmedcentralcanada.ca)
  • 15-d-Δ12,14-PGJ2, Δ12-PGJ2, and PGJ2 share a common mono-unsaturated cyclopentenone structure as well as a set of similar biological activities including the ability to suppress inflammation responses and the growth as well as survival of cells, particularly those of cancerous or neurological origin. (wikipedia.org)
  • cancers
  • CTLA-4 is found on the surface of T cells, and cancers use this switch to turn off the body's anti-cancer immune responses. (cancernetwork.com)
  • http://cancerres.aacrjournals.org/cgi/content/full/66/16/8147 "Frequent Alterations in the Expression of Serine/Threonine Kinases in Human Cancers" Capra et al. (wikipedia.org)
  • Molecule
  • 1), CD28 , RGMb (repulsive guidance molecule family member b), and CTLA-4 (cyto-toxic T lymphocyte antigen-4) are only some of the players. (thefreedictionary.com)
  • They each have an N-terminal signal peptide of 20-30 amino acids that they require for secretion from a cell, a pro-region called latency associated peptide (LAP - Alias: Pro-TGF beta 1, LAP/TGF beta 1), and a 112-114 amino acid C-terminal region that becomes the mature TGF-β molecule following its release from the pro-region by proteolytic cleavage. (wikipedia.org)
  • regulate
  • Inflammatory mediators and the presence of bacterial products at the foci of infection regulate the function and life span of these cells. (openthesis.org)
  • Members of the TLR family were detected on glia, neurons and on neural progenitor cells in which they regulate cell-fate decision. (wikipedia.org)
  • NSCLC
  • An investigational new drug application has been approved by the China Food and Drug Administration (CFDA), and two Phase 1 trials are ongoing in China - non-small cell lung cancer (NSCLC) (NCT02896231) and high grade gliomas with PTPRZ1-MET fusion gene (NCT02978261). (businesswire.com)
  • TUSC2 is a tumor suppressor gene that is lacking in cancer cells of many different cancer types, including non-small cell lung cancer (NSCLC). (pipelinereview.com)
  • Genprex is utilizing its proprietary gene therapy platform to develop Oncoprex as a targeted treatment option suitable for a majority of non-small cell lung cancer (NSCLC) patients. (pipelinereview.com)
  • macrophages
  • TGF-β is secreted by many cell types, including macrophages, in a latent form in which it is complexed with two other polypeptides, latent TGF-beta binding protein (LTBP) and latency-associated peptide (LAP). (wikipedia.org)
  • For example, preincubation of macrophages with apoptotic cells strongly suppresses the inflammatory response induced via Toll-like receptor 4 by lipopolysaccharide, a component of the cell wall of Gram-negative bacteria ( 4 - 6 ). (pubmedcentralcanada.ca)
  • They are single, membrane-spanning, non-catalytic receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize structurally conserved molecules derived from microbes. (wikipedia.org)
  • tumour
  • Cancer cell heterogeneity, or tumour heterogeneity, is the idea that tumours are made up of different populations of cancer cells that are morphologically, phenotypically and functionally different. (wikipedia.org)
  • Antineoplastic drugs kill susceptible sub-populations and the tumour mass may shrink as an initial response to the drug, resistant cancer cells will survive treatment, be selected and then propagate, eventually causing a cancer relapse. (wikipedia.org)
  • Cancer cell heterogeneity can cause disease progression when molecularly targeted therapy, fails to kill those tumor cells which do not express the marker, then divide and mutate further, creating a new heterogeneous tumour. (wikipedia.org)
  • Expression
  • Upregulation of DR5 by EEDS was mediated by an endoplasmic reticulum stress-induced transcription factor, CCAAT/enhancer-binding protein homologous protein (CHOP), and knockdown of CHOP expression inhibited EEDS-induced DR5 upregulation and abolished the EEDS-associated increase in TRAIL toxicity in A549 cells. (biomedcentral.com)
  • No expression of Daxx leads to malfunction of S phase and cells with two nuclei are formed. (wikipedia.org)
  • DLC1 expression is frequently lost in tumor cells, resulting in constitutive activation of the RhoGTPases RhoA and Cdc42. (wikipedia.org)
  • Of the latter, types include: Serine/threonine kinase (STK) expression is altered in many types of cancer. (wikipedia.org)
  • Cyclic stretching of human tendon fibroblasts stimulated the expression and release of ANGPTL4 protein via TGF-β and HIF-1α signalling, and the released ANGPTL4 was pro-angiogenic. (wikipedia.org)
  • therapies
  • Anti-angiogenic therapies have several noted immunostimulatory effects including increased trafficking of T cells into tumors, and reduction of immunosuppressive cytokines and T regulatory cells, suggesting anti-angiogenic therapies may complement subsequent or concurrent immunostimulatory therapies. (phacilitate.co.uk)
  • Current standard cancer therapies involve surgery to remove the major tumor masses and subsequent radiotherapy and/or chemotherapy to kill potential remaining cancer cells and to prevent cancer recurrence. (biomedcentral.com)
  • Regenerative medicine relying on cell and gene therapies is one of the most promising approaches to repair tissues. (biomedcentral.com)
  • Antineoplastic resistance, often used interchangeably with chemotherapy resistance, is the multiple drug resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies. (wikipedia.org)
  • Antineoplastic resistance, synonymous with chemotherapy resistance, is the ability of cancer cells to survive and grow despite different anti-cancer therapies, i.e. their multiple drug resistance. (wikipedia.org)