Abstract：
:Adaptive therapy seeks to exploit intra-tumoral competition to avoid, or at least delay, the emergence of therapy resistance in cancer. Motivated by promising results in prostate cancer, there is growing interest in extending this approach to other neoplasms. As such, it is urgent to understand the characteristics of a cancer which determine whether or not it will respond well to adaptive therapy. A plausible candidate for such a selection criterion is the fitness cost of resistance. In this paper, we study a general but simple mathematical model to investigate whether the presence of a cost is necessary for adaptive therapy to extend the time to progression beyond that of a standard-of-care continuous therapy. Tumor cells were divided into sensitive and resistant populations and we model their competition using a system of two ordinary differential equations based on the Lotka-Volterra model. For tumors close to their environmental carrying capacity a cost was not required. However, for tumors growing far from carrying capacity, a cost may be required to see meaningful gains. Notably, it is important to consider cell turnover in the tumor, and we discuss its role in modulating the impact of a resistance cost. To conclude, we present evidence for the predicted cost-turnover interplay in data from 67 prostate cancer patients undergoing intermittent androgen deprivation therapy. Our work helps to clarify under which circumstances adaptive therapy may be beneficial and suggests that turnover may play an unexpectedly important role in the decision making process.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Strobl MAR,West J,Viossat Y,Damaghi M,Robertson-Tessi M,Brown JS,Gatenby RA,Maini PK,Anderson ARAdoi
10.1158/0008-5472.CAN-20-0806subject
Has Abstractpub_date
2020-11-10 00:00:00eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-20-0806pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:Chromosomal rearrangements involving receptor tyrosine kinases (RTK) are a clinically relevant oncogenic mechanism in human cancers. These chimeric oncoproteins often contain the C-terminal kinase domain of the RTK joined in cis to various N-terminal, nonkinase fusion partners. The functional role of the N-terminal fu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-18-1492
更新日期：2019-02-01 00:00:00
abstract：:The activity of an endonuclease(s) acting on double-stranded, ultraviolet-irradiated, and 2-acetylaminofluorene-bound DNA but not on double-stranded undamaged DNA triples within two hr after partial hepatectomy. Although the activity drops between four and six hr after operation, it remains above levels measured in li...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-06-01 00:00:00
abstract：:Molecular docking is a standard computational approach to predict binding modes of protein-ligand complexes by exploring alternative orientations and conformations of the ligand (i.e., by exploring ligand flexibility). Docking tools are largely used for virtual screening of small drug-like molecules, but their accurac...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-0511
更新日期：2017-11-01 00:00:00
abstract：:The enhancer pioneer transcription factor FoxA1 is a global mediator of steroid receptor (SR) action in hormone-dependent cancers. In castration-resistant prostate cancer (CRPC), FoxA1 acts as an androgen receptor cofactor to drive G₂ to M-phase cell-cycle transit. Here, we describe a mechanistically distinct SR-indep...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-1882
更新日期：2011-11-01 00:00:00
abstract：:Prostate cancer has become epidemic, and environmental factors such as cadmium may be partly responsible. This study reports malignant transformation of the nontumorigenic human prostatic epithelial cell line RWPE-1 by in vitro cadmium exposure. The cadmium-transformed cells exhibited a loss of contact inhibition in v...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2001-01-15 00:00:00
abstract：:Promoter methylation of the mismatch repair gene plays a key role in sporadic microsatellite instability (MSI) colorectal cancers. However, promoter methylation often occurs in proximal colon cancers, and molecular phenotypes underlying MSI cancers in distal colon have not been fully clarified. Our goal was to clarify...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-06-1163
更新日期：2006-10-15 00:00:00
abstract：:Oxidative stress exerted by superoxide-generating (redox-cycling) agents such as paraquat triggers the soxRS regulon of Escherichia coli. In this system, SoxR protein is the redox-sensitive activator of the soxS gene, the product of which then activates the approximately 10 promoters of this regulon. We found that 4-n...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1993-07-15 00:00:00
abstract：:A low molecular weight cytoplasmic protein (Mr 19,000-22,000) has been reported to be overexpressed in some multidrug-resistant cells. We have found that a cytoplasmic protein with a molecular weight of 22,000 is highly expressed in the human myelogenous leukemia K562 cells resistant to Adriamycin (K562/ADM). The Mr 2...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-06-01 00:00:00
abstract：:Of six prostatic carcinoma cell lines examined (ALVA31, DU145, JCA1, LNCaP, ND1, and PC3) by flow cytometric analysis, all were found to be positive for Fas antigen. Furthermore, of the prostate tissue specimens studied (six cases), all revealed Fas expression in benign and malignant epithelial cells. The agonistic an...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-05-01 00:00:00
abstract：:Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here, we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 μm) ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-2942
更新日期：2017-05-01 00:00:00
abstract：:Phosphoglycerate dehydrogenase (PHGDH) is the metabolic enzyme responsible for shunting the glycolytic intermediate 3-phosphoglycerate to the serine synthesis pathway. In breast cancer and several other types of cancer, increased PHGDH expression is associated with patient mortality. Early studies focused on the role ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-16-1730
更新日期：2016-11-15 00:00:00
abstract：:The effect of schedule of drug administration on the biochemical and therapeutic effects of the combination of 1-beta-D-arabinofuranosylcytosine (ara-C) and asparaginase was investigated in vivo and in vitro using the murine leukemia L5178Y. Treatment of cells in vitro with either ara-C (10(-6) M) or asparaginase (0.5...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-06-01 00:00:00
abstract：:Alterations in the expression of the epidermal growth factor (EGF) receptor ErbB family are frequently encountered in a number of human cancers. Two of these receptors, ErbB3 and ErbB4, are known to bind a family of related proteins termed heregulins (HRGs) or neu differentiation factors. In biologically relevant syst...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-03-15 00:00:00
abstract：:Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here, we report the elucidation of the biological characteristics of the two most prevalent uterine leiomyoma subtypes, MED12-mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) uterine leiomyomas. Because...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-1744
更新日期：2017-12-15 00:00:00
abstract：:8-Carbamoyl-3-(2-chloroethyl)imidazo[5,1-d]-1,2,3,5-tetrazin-4(3H) -one (mitozolomide) demonstrates curative action against a range of murine tumor model systems. At single doses of between 20 and 40 mg/kg, the latter of which approximates the 10% lethal dose value in mice, the compound elicited cures against the L121...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Predisposition to prostate cancer has a genetic component, and there are reports of familial clustering of breast and prostate cancer. Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectiv...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-08-15 00:00:00
abstract：:Mesothelioma is a unique and insidious tumor associated historically with occupational exposure to asbestos. The transcription factor, activator protein-1 (AP-1) is a major target of asbestos-induced signaling pathways. Here, we demonstrate that asbestos-induced mesothelial cell transformation is linked to increases i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2002-11-01 00:00:00
abstract：:The kinetic properties of a soluble, magnesium-dependent 5'-nucleotidase from human malignant lymphocytes have been determined. The partially purified enzyme is distinct from plasma membrane-associated 5'-nucleotidase and is free of nonspecific phosphatase activity. Among purine ribonucleotides, it reacted efficiently...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:Bifunctional alkylating agents are known to cross-link DNA by simultaneously alkylating two guanine residues located on opposite strands. Despite this apparent requirement for bifunctionality, 1-(2-chloroethyl)-1-nitrosoureas bearing a single alkylating function were found to cross-link DNA in vitro. Cross-linking was...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1977-05-01 00:00:00
abstract：:CD44 is an integral membrane glycoprotein that functions as a receptor for the extracellular matrix glycan, hyaluronan. Here we report that CD44 is a novel biomarker for non-small cell lung tumors, squamous metaplasia of the lung, and activated type II pneumocytes. We have examined the expression of CD44 in 12 human l...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-03-01 00:00:00
abstract：:Neuropilin-1 (NP1), in conjunction with plexins, promotes axon repulsion by binding to semaphorin 3A (SEMA3A). Although NP1 is expressed in carcinoma cells, its functions have remained elusive, and neither SEMA3A nor plexin expression has been explored in cancer. Here we provide evidence that breast carcinoma cells su...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-09-01 00:00:00
abstract：:A cloned, virus-producing, tumorigenic, promonocytic leukemia cell line, AC8, derived from an Abelson murine leukemia virus-infected mouse can differentiate in vitro. Differentiated cells, purified from a population containing undifferentiated cells on the basis of expression of the macrophage differentiation antigens...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
abstract：:Our recent allelic analysis of head and neck squamous cell carcinomas identified a high incidence of chromosomal loss on 13q. To further define an area of minimal loss, we tested 60 primary head and neck squamous cell carcinomas in 59 patients for loss of heterozygosity (LOH) by using 10 polymorphic microsatellite mar...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1994-09-01 00:00:00
abstract：:The formation of tumors in adult nude mice from transformed human mammary epithelial cells was drastically inhibited (greater than 80%) both after coinjection of tumoral cells and virus or after a single s.c. injection of parvovirus H-1 at the site of cell implantation prior to tumor formation. Moreover, when injected...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-06-15 00:00:00
abstract：:A family of cell surface glycoproteins with a molecular weight of 96,000 (gp96) has recently been implicated in the individually distinct immunogenicity of chemically induced sarcomas of inbred mice. Rabbit antiserum to murine gp96 detects an antigenically related Mr 96,000 cell surface glycoprotein on two cultured hu...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1989-03-15 00:00:00
abstract：:Hypoxia inducible factors (HIF) are critical mediators of the cellular response to decreased oxygen tension and are overexpressed in a number of tumors. Although HIF1alpha and HIF2alpha share a high degree of sequence homology, recent work has shown that the two alpha subunits can have contrasting and tissue-specific ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-08-4223
更新日期：2009-04-01 00:00:00
abstract：:Comparison of the cell surface characteristics of the parental strain-specific TA3-St ascites cell (I) of the strain A mouse and the more allotransplantable TA3-St/ticol ascites cell (II), immunoselected for reduced absorption of anti-H-2a antibody from Cell I, revealed the following. Cell II, like Cell I, possessed n...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-09-01 00:00:00
abstract：:Using the phage lambdaLIZ-based transgenic in vivo mutagenesis assay, mean mutant rates were determined in the spleen of mice exposed to sustained oxidative stress and were found to be increased approximately 3-fold in plasmacytoma-susceptible BALB/c and C.D2-Idh1-Pep3 mice, but not in plasmacytoma-resistant DBA/2N mi...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1998-04-15 00:00:00
abstract：:While showing promise, vaccination strategies to treat cancer require further optimization. Likely barriers to efficacy involve cancer-associated immunosuppression and peripheral tolerance, which limit the generation of effective vaccine-specific cytotoxic T lymphocytes (CTL). Because CD4(+) T cells improve CTL respon...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-15-3130
更新日期：2016-05-15 00:00:00
abstract：:The MCT-1 oncogene was originally identified from lymphoma cell lines. Herein we establish that MCT-1 is highly expressed in 85% of human diffuse large B-cell lymphomas (DLBCL) and that knocking down MCT-1 by a specific short hairpin RNA in DLBCL cells induces apoptosis, supporting a critical role for MCT-1 in DLBCL c...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-09-1606
更新日期：2009-10-01 00:00:00
