A framework for understanding and targeting residual disease in oncogene-driven solid cancers.

Abstract:

:Molecular targeted therapy has the potential to dramatically improve survival in patients with cancer. However, complete and durable responses to targeted therapy are rare in individuals with advanced-stage solid cancers. Even the most effective targeted therapies generally do not induce a complete tumor response, resulting in residual disease and tumor progression that limits patient survival. We discuss the emerging need to more fully understand the molecular basis of residual disease as a prelude to designing therapeutic strategies to minimize or eliminate residual disease so that we can move from temporary to chronic control of disease, or a cure, for patients with advanced-stage solid cancers. Ultimately, we propose a shift from the current reactive paradigm of analyzing and treating acquired drug resistance to a pre-emptive paradigm of defining the mechanisms that result in residual disease, to target and limit this disease reservoir.

journal_name

Nat Med

journal_title

Nature medicine

authors

Bivona TG,Doebele RC

doi

10.1038/nm.4091

subject

Has Abstract

pub_date

2016-05-05 00:00:00

pages

472-8

issue

5

eissn

1078-8956

issn

1546-170X

pii

nm.4091

journal_volume

22

pub_type

杂志文章
  • Nociceptor sensitization in pain pathogenesis.

    abstract::The incidence of chronic pain is estimated to be 20-25% worldwide. Few patients with chronic pain obtain complete relief from the drugs that are currently available, and more than half report inadequate relief. Underlying the challenge of developing better drugs to manage chronic pain is incomplete understanding of th...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2235

    authors: Gold MS,Gebhart GF

    更新日期:2010-11-01 00:00:00

  • Targeting wild-type KRAS-amplified gastroesophageal cancer through combined MEK and SHP2 inhibition.

    abstract::The role of KRAS, when activated through canonical mutations, has been well established in cancer1. Here we explore a secondary means of KRAS activation in cancer: focal high-level amplification of the KRAS gene in the absence of coding mutations. These amplifications occur most commonly in esophageal, gastric and ova...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0022-x

    authors: Wong GS,Zhou J,Liu JB,Wu Z,Xu X,Li T,Xu D,Schumacher SE,Puschhof J,McFarland J,Zou C,Dulak A,Henderson L,Xu P,O'Day E,Rendak R,Liao WL,Cecchi F,Hembrough T,Schwartz S,Szeto C,Rustgi AK,Wong KK,Diehl JA,Jen

    更新日期:2018-07-01 00:00:00

  • Age and generational patterns of overdose death risk from opioids and other drugs.

    abstract::The ongoing substance misuse epidemic in the United States is complex and dynamic and should be approached as such in the development and evaluation of policy1. Drug overdose deaths (largely attributable to opioid misuse) in the United States have grown exponentially for almost four decades, but the mechanisms of this...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-020-0855-y

    authors: Jalal H,Buchanich JM,Sinclair DR,Roberts MS,Burke DS

    更新日期:2020-05-01 00:00:00

  • Targeted estrogen delivery reverses the metabolic syndrome.

    abstract::We report the development of a new combinatorial approach that allows for peptide-mediated selective tissue targeting of nuclear hormone pharmacology while eliminating adverse effects in other tissues. Specifically, we report the development of a glucagon-like peptide-1 (GLP-1)-estrogen conjugate that has superior sex...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3009

    authors: Finan B,Yang B,Ottaway N,Stemmer K,Müller TD,Yi CX,Habegger K,Schriever SC,García-Cáceres C,Kabra DG,Hembree J,Holland J,Raver C,Seeley RJ,Hans W,Irmler M,Beckers J,de Angelis MH,Tiano JP,Mauvais-Jarvis F,Perez-Ti

    更新日期:2012-12-01 00:00:00

  • A critical developmental switch defines the kinetics of kidney cyst formation after loss of Pkd1.

    abstract::Autosomal dominant polycystic kidney disease is an important cause of end-stage renal disease, for which there is no proven therapy. Mutations in PKD1 (the gene encoding polycystin-1) are the principal cause of this disease. The disease begins in utero and is slowly progressive, but it is not known whether cystogenesi...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1675

    authors: Piontek K,Menezes LF,Garcia-Gonzalez MA,Huso DL,Germino GG

    更新日期:2007-12-01 00:00:00

  • Chip-NMR biosensor for detection and molecular analysis of cells.

    abstract::Rapid and accurate measurement of biomarkers in tissue and fluid samples is a major challenge in medicine. Here we report the development of a new, miniaturized diagnostic magnetic resonance (DMR) system for multiplexed, quantitative and rapid analysis. By using magnetic particles as a proximity sensor to amplify mole...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.1711

    authors: Lee H,Sun E,Ham D,Weissleder R

    更新日期:2008-08-01 00:00:00

  • Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation.

    abstract::Transplantation of xenogeneic hepatocytes would provide a novel therapy for liver disease and would help to solve the problem of an insufficient supply of donor organs. We have tested whether xenogeneic cells infused into the liver could correct the metabolic defect in the Watanable heritable hyperlipidemic (WHHL) rab...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0197-48

    authors: Gunsalus JR,Brady DA,Coulter SM,Gray BM,Edge AS

    更新日期:1997-01-01 00:00:00

  • A victory for genes.

    abstract::The ability to patent human genes has been costly to researchers and patients, and has restricted competition in the biotech marketplace. The recent US Supreme Court decision making isolated human genes unpatentable will bring freedom of choice to the patient, and level the playing field for research and development. ...

    journal_title:Nature medicine

    pub_type: 社论

    doi:10.1038/nm.3279

    authors:

    更新日期:2013-07-01 00:00:00

  • The activated conformation of integrin β7 is a novel multiple myeloma-specific target for CAR T cell therapy.

    abstract::Cancer-specific cell-surface antigens are ideal targets for monoclonal antibody (mAb)-based immunotherapy but are likely to have previously been identified in transcriptome or proteome analyses. Here, we show that the active conformer of an integrin can serve as a specific therapeutic target for multiple myeloma (MM)....

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4431

    authors: Hosen N,Matsunaga Y,Hasegawa K,Matsuno H,Nakamura Y,Makita M,Watanabe K,Yoshida M,Satoh K,Morimoto S,Fujiki F,Nakajima H,Nakata J,Nishida S,Tsuboi A,Oka Y,Manabe M,Ichihara H,Aoyama Y,Mugitani A,Nakao T,Hino M,

    更新日期:2017-12-01 00:00:00

  • Inducer-stimulated Fas targets activated endothelium for destruction by anti-angiogenic thrombospondin-1 and pigment epithelium-derived factor.

    abstract::Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-media...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm0402-349

    authors: Volpert OV,Zaichuk T,Zhou W,Reiher F,Ferguson TA,Stuart PM,Amin M,Bouck NP

    更新日期:2002-04-01 00:00:00

  • Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma.

    abstract::Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responde...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4401

    authors: Tan DSW,Chong FT,Leong HS,Toh SY,Lau DP,Kwang XL,Zhang X,Sundaram GM,Tan GS,Chang MM,Chua BT,Lim WT,Tan EH,Ang MK,Lim TKH,Sampath P,Chowbay B,Skanderup AJ,DasGupta R,Iyer NG

    更新日期:2017-10-01 00:00:00

  • CITED2 links hormonal signaling to PGC-1α acetylation in the regulation of gluconeogenesis.

    abstract::During fasting, induction of hepatic gluconeogenesis is crucial to ensure proper energy homeostasis. Such induction is dysregulated in type 2 diabetes, resulting in the development of fasting hyperglycemia. Hormonal and nutrient regulation of metabolic adaptation during fasting is mediated predominantly by the transcr...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2691

    authors: Sakai M,Matsumoto M,Tujimura T,Yongheng C,Noguchi T,Inagaki K,Inoue H,Hosooka T,Takazawa K,Kido Y,Yasuda K,Hiramatsu R,Matsuki Y,Kasuga M

    更新日期:2012-03-18 00:00:00

  • Notch3 signaling promotes the development of pulmonary arterial hypertension.

    abstract::Notch receptor signaling is implicated in controlling smooth muscle cell proliferation and in maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension is characterized by excessive vascular resistance, smooth muscle cell proliferation in small pulmonary arteries, leading to elevati...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2021

    authors: Li X,Zhang X,Leathers R,Makino A,Huang C,Parsa P,Macias J,Yuan JX,Jamieson SW,Thistlethwaite PA

    更新日期:2009-11-01 00:00:00

  • Inflammasome-derived IL-1β production induces nitric oxide-mediated resistance to Leishmania.

    abstract::Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3221

    authors: Lima-Junior DS,Costa DL,Carregaro V,Cunha LD,Silva AL,Mineo TW,Gutierrez FR,Bellio M,Bortoluci KR,Flavell RA,Bozza MT,Silva JS,Zamboni DS

    更新日期:2013-07-01 00:00:00

  • Author Correction: A SARS-like cluster of circulating bat coronaviruses shows potential for human emergence.

    abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

    journal_title:Nature medicine

    pub_type: 已发布勘误

    doi:10.1038/s41591-020-0924-2

    authors: Menachery VD,Yount BL Jr,Debbink K,Agnihothram S,Gralinski LE,Plante JA,Graham RL,Scobey T,Ge XY,Donaldson EF,Randell SH,Lanzavecchia A,Marasco WA,Shi ZL,Baric RS

    更新日期:2020-07-01 00:00:00

  • Passive immunization with a human monoclonal antibody protects hu-PBL-SCID mice against challenge by primary isolates of HIV-1.

    abstract::How well antibodies can protect against disease due to HIV-1 infection remains a pivotal but unresolved issue with important implications for vaccine design and the use of prophylactic antibody to prevent infection after accidental exposure to the virus and to interrupt transmission of virus from mother to child. Stro...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1297-1389

    authors: Gauduin MC,Parren PW,Weir R,Barbas CF,Burton DR,Koup RA

    更新日期:1997-12-01 00:00:00

  • The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif.

    abstract::The human protein apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamina...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm945

    authors: Sheehy AM,Gaddis NC,Malim MH

    更新日期:2003-11-01 00:00:00

  • Neoadjuvant nivolumab modifies the tumor immune microenvironment in resectable glioblastoma.

    abstract::Glioblastoma is the most common primary central nervous system malignancy and has a poor prognosis. Standard first-line treatment, which includes surgery followed by adjuvant radio-chemotherapy, produces only modest benefits to survival1,2. Here, to explore the feasibility, safety and immunobiological effects of PD-1 ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-018-0339-5

    authors: Schalper KA,Rodriguez-Ruiz ME,Diez-Valle R,López-Janeiro A,Porciuncula A,Idoate MA,Inogés S,de Andrea C,López-Diaz de Cerio A,Tejada S,Berraondo P,Villarroel-Espindola F,Choi J,Gúrpide A,Giraldez M,Goicoechea I,Gallego Pe

    更新日期:2019-03-01 00:00:00

  • A new activity for SAMHD1 in HIV restriction.

    abstract::Restriction factors are host cell proteins that inhibit retroviral infection. A new study using mutants of human HIV-1 restriction factor SAMHD1 suggests that it inhibits infection through degradation of viral RNA rather than through its dNTPase activity as previously suggested. ...

    journal_title:Nature medicine

    pub_type: 评论,杂志文章

    doi:10.1038/nm.3657

    authors: Yang Z,Greene WC

    更新日期:2014-08-01 00:00:00

  • Human 3D cellular model of hypoxic brain injury of prematurity.

    abstract::Owing to recent medical and technological advances in neonatal care, infants born extremely premature have increased survival rates1,2. After birth, these infants are at high risk of hypoxic episodes because of lung immaturity, hypotension and lack of cerebral-flow regulation, and can develop a severe condition called...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/s41591-019-0436-0

    authors: Pașca AM,Park JY,Shin HW,Qi Q,Revah O,Krasnoff R,O'Hara R,Willsey AJ,Palmer TD,Pașca SP

    更新日期:2019-05-01 00:00:00

  • A cannabinoid mechanism in relapse to cocaine seeking.

    abstract::Treatment of cocaine addiction is hampered by high rates of relapse even after prolonged drug abstinence. This relapse to compulsive cocaine use can be triggered by re-exposure to cocaine, by re-exposure to stimuli previously associated with cocaine or by exposure to stress. In laboratory rats, similar events reinstat...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1001-1151

    authors: De Vries TJ,Shaham Y,Homberg JR,Crombag H,Schuurman K,Dieben J,Vanderschuren LJ,Schoffelmeer AN

    更新日期:2001-10-01 00:00:00

  • Epigenetic modulation of the renal β-adrenergic-WNK4 pathway in salt-sensitive hypertension.

    abstract::How high salt intake increases blood pressure is a key question in the study of hypertension. Salt intake induces increased renal sympathetic activity resulting in sodium retention. However, the mechanisms underlying the sympathetic control of renal sodium excretion remain unclear. In this study, we found that β(2)-ad...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2337

    authors: Mu S,Shimosawa T,Ogura S,Wang H,Uetake Y,Kawakami-Mori F,Marumo T,Yatomi Y,Geller DS,Tanaka H,Fujita T

    更新日期:2011-05-01 00:00:00

  • PTEN opposes negative selection and enables oncogenic transformation of pre-B cells.

    abstract::Phosphatase and tensin homolog (PTEN) is a negative regulator of the phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) signaling pathway and a potent tumor suppressor in many types of cancer. To test a tumor suppressive role for PTEN in pre-B acute lymphoblastic leukemia (ALL), we induced Cre-mediated de...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4062

    authors: Shojaee S,Chan LN,Buchner M,Cazzaniga V,Cosgun KN,Geng H,Qiu YH,von Minden MD,Ernst T,Hochhaus A,Cazzaniga G,Melnick A,Kornblau SM,Graeber TG,Wu H,Jumaa H,Müschen M

    更新日期:2016-04-01 00:00:00

  • Emerging cytopathic and antigenic simian immunodeficiency virus variants influence AIDS progression.

    abstract::Genetic variants of human and simian immunodeficiency virus (HIV and SIV) that evolve during the course of infection and progression to AIDS are phenotypically and antigenically distinct from their progenitor viruses present at early stages of infection. However, it has been unclear how these late variants, which are ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/8414

    authors: Kimata JT,Kuller L,Anderson DB,Dailey P,Overbaugh J

    更新日期:1999-05-01 00:00:00

  • Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

    abstract::Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm1097-1150

    authors: Vígh L,Literáti PN,Horváth I,Török Z,Balogh G,Glatz A,Kovács E,Boros I,Ferdinándy P,Farkas B,Jaszlits L,Jednákovits A,Korányi L,Maresca B

    更新日期:1997-10-01 00:00:00

  • A negative regulator of MAP kinase causes depressive behavior.

    abstract::The lifetime prevalence (∼16%) and the economic burden ($100 billion annually) associated with major depressive disorder (MDD) make it one of the most common and debilitating neurobiological illnesses. To date, the exact cellular and molecular mechanisms underlying the pathophysiology of MDD have not been identified. ...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.2219

    authors: Duric V,Banasr M,Licznerski P,Schmidt HD,Stockmeier CA,Simen AA,Newton SS,Duman RS

    更新日期:2010-11-01 00:00:00

  • Translational value of mouse models in oncology drug development.

    abstract::Much has been written about the advantages and disadvantages of various oncology model systems, with the overall finding that these models lack the predictive power required to translate preclinical efficacy into clinical activity. Despite assertions that some preclinical model systems are superior to others, no singl...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.3853

    authors: Gould SE,Junttila MR,de Sauvage FJ

    更新日期:2015-05-01 00:00:00

  • Genetic clues to the pathogenesis of Parkinson's disease.

    abstract::Recent years have seen an explosion in the rate of discovery of genetic defects linked to Parkinson's disease. These breakthroughs have not provided a direct explanation for the disease process. Nevertheless, they have helped transform Parkinson's disease research by providing tangible clues to the neurobiology of the...

    journal_title:Nature medicine

    pub_type: 杂志文章,评审

    doi:10.1038/nm1068

    authors: Vila M,Przedborski S

    更新日期:2004-07-01 00:00:00

  • A novel chimeric antigen receptor containing a JAK-STAT signaling domain mediates superior antitumor effects.

    abstract::The adoptive transfer of T cells engineered with a chimeric antigen receptor (CAR) (hereafter referred to as CAR-T cells) specific for the B lymphocyte antigen CD19 has shown impressive clinical responses in patients with refractory B cell malignancies. However, the therapeutic effects of CAR-T cells that target other...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/nm.4478

    authors: Kagoya Y,Tanaka S,Guo T,Anczurowski M,Wang CH,Saso K,Butler MO,Minden MD,Hirano N

    更新日期:2018-03-01 00:00:00

  • The pathogenesis of familial hypertrophic cardiomyopathy: early and evolving effects from an alpha-cardiac myosin heavy chain missense mutation.

    abstract::Familial hypertrophic cardiomyopathy (FHC) is a genetic disorder resulting from mutations in genes encoding sarcomeric proteins. This typically induces hyperdynamic ejection, impaired relaxation, delayed early filling, myocyte disarray and fibrosis, and increased chamber end-systolic stiffness. To better understand th...

    journal_title:Nature medicine

    pub_type: 杂志文章

    doi:10.1038/6549

    authors: Georgakopoulos D,Christe ME,Giewat M,Seidman CM,Seidman JG,Kass DA

    更新日期:1999-03-01 00:00:00