Tumor heterogeneity: does it matter?

Abstract:

:Introduction: It has long been recognized that tumors are composed of a mosaic of cells and numerous methods have been developed to detect tumor heterogeneity, including in situ hybridization, multi-regional sampling, cytological assays, and whole genome and single cell sequencing. Using these methods, heterogeneity has been observed at the genetic, epigenetic, and phenotypic level in numerous cancers. With the advent of deep sequencing technology, we now appreciate a greater complexity of distinct genotypes and phenotypes that drive the biological behavior of cancer. Despite decades of progress in detecting tumor heterogeneity, the question remains: to what extent does it matter? Areas covered: This review explores the evidence for and against the importance of tumor heterogeneity in three main areas: prognostication, development of targeted therapeutics and tumor resistance; summarizing current understanding before evaluating ongoing experimental and clinical developments. Expert opinion: Theoretical understanding and in vitro detection of intratumour heterogeneity promises much but is yet to translate into meaningful clinical benefit. However, the recent emergence of a host of technological innovations and upcoming clinical trials may soon change the landscape of this field.

authors

Turnquist C,Watson RA,Protheroe A,Verrill C,Sivakumar S

doi

10.1080/14737140.2019.1667236

subject

Has Abstract

pub_date

2019-10-01 00:00:00

pages

857-867

issue

10

eissn

1473-7140

issn

1744-8328

journal_volume

19

pub_type

杂志文章,评审
  • Determining treatment intensity in elderly patients with multiple myeloma.

    abstract:INTRODUCTION:In the majority of cases, multiple myeloma is a disease occurring in elderly patients. In the last decades, a major improvement in myeloma patients' outcome has been achieved with the introduction of several new drugs. However, this positive outcome was less likely to occur in elderly patients. Areas cover...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1080/14737140.2018.1496823

    authors: Salvini M,D'Agostino M,Bonello F,Boccadoro M,Bringhen S

    更新日期:2018-09-01 00:00:00

  • Individualized cancer therapy: molecular approaches to the prediction of tumor response.

    abstract::A major issue with current cancer therapy is how to ensure the maximum benefit with minimum toxicity for individual patients. With the progress of the human genome project have come high-throughput technologies for the analysis of DNA, gene expression or tumor protein in an efficient and quantitative manner. This revi...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.2.1.113

    authors: McLeod HL

    更新日期:2002-02-01 00:00:00

  • Emerging personalized approaches for the management of advanced urothelial carcinoma.

    abstract::Urothelial carcinoma of the bladder comprises a spectrum of illnesses ranging from nonmuscle-invasive to muscle-invasive to advanced/metastatic disease. Each of these clinical states is characterized by a unique pathogenesis, prognosis and approach to treatment. However, given the heterogeneity of urothelial carcinoma...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/era.12.141

    authors: Tsao CK,Gartrell BA,Oh WK,Galsky MD

    更新日期:2012-12-01 00:00:00

  • Prostate-sparing cystectomy: has Pandora's box been opened?

    abstract::En bloc removal of the prostate has traditionally been an integral component of radical cystectomy for men with bladder cancer owing to a high incidence of occult prostatic malignancy. However, the risk of functional morbidity following this procedure is considerable and can delay patient acceptance of cystectomy, whi...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.7.7.1003

    authors: Kefer JC,Cherullo EE,Jones JS,Gong MC,Campbell SC

    更新日期:2007-07-01 00:00:00

  • Unnatural killer cells to prevent bloodborne metastasis: inspiration from biology and engineering.

    abstract::Metastasis contributes to over 90% of cancer-related deaths. Many types of cancer metastasize via the bloodstream, where circulating tumor cells (CTCs) originating from the primary tumor can undergo selectin-mediated adhesion with the blood vessel wall and subsequently transmigrate to anatomically distant organs. In a...

    journal_title:Expert review of anticancer therapy

    pub_type: 社论

    doi:10.1586/14737140.2014.916619

    authors: Mitchell MJ,King MR

    更新日期:2014-06-01 00:00:00

  • Anticancer drug development based on modulation of the Bcl-2 family core apoptosis mechanism.

    abstract::Cancer cells generally maintain their survival by suppressing apoptosis. Mitochondrial mechanisms are involved in most forms of apoptosis (referred to as mitochondrial apoptosis), and the Bcl-2 family controls apoptosis at the mitochondrion via a balance of the effects of pro- and antiapoptotic members. Antiapoptotic ...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.4.6.1157

    authors: Gardner CR

    更新日期:2004-12-01 00:00:00

  • Primary and secondary therapeutic strategies for EGF receptor pathway inhibition in non-small-cell lung cancer.

    abstract::As diagnostic and therapeutic options increase, strategies for the treatment of non-small-cell lung cancer (NSCLC) are becoming more tailored for specific patient subpopulations and individual patients. The introduction of therapy targeted against the EGF receptor (EGFR) pathway has provided new treatment options for ...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/era.10.104

    authors: Batus M,Fidler MJ,Bonomi PD

    更新日期:2010-10-01 00:00:00

  • Advances in diagnosis and management of oligodendroglioma.

    abstract::Oligodendrogliomas are primary brain tumors, genetically characterized by chromosomal alterations in the 1p and 19q. Recent clinical trials have shown that oligodendrogliomas are sensitive to PCV chemotherapy with 60-65% of patients responding and median response duration of 1-1.5 years. The response rate in mixed oli...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.2.5.520

    authors: Hussein MR,Baidas S

    更新日期:2002-10-01 00:00:00

  • Optimizing treatment of metastatic renal cell carcinoma by changing mechanism of action.

    abstract::Novel targeted agents, such as VEGF receptor-tyrosine kinase inhibitors (VEGFR-TKIs) and mTOR inhibitors, have improved therapy for metastatic renal cell carcinoma. Sequential administration of agents with similar mechanisms of action has shown some efficacy in small retrospective studies; however, prospective Phase I...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/era.11.21

    authors: Larkin J,Swanton C,Pickering L

    更新日期:2011-04-01 00:00:00

  • Temozolomide: a novel oral alkylating agent.

    abstract::Temozolomide is an imidazotetrazine with a mechanism of action and efficacy similar to dacarbazine (DTIC). However, it differs from DTIC in that it can be taken orally, degrades spontaneously to an active metabolite and penetrates the blood-brain barrier. It is well tolerated, making it a suitable candidate for combin...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.1.1.13

    authors: Danson SJ,Middleton MR

    更新日期:2001-06-01 00:00:00

  • Surgical management of bladder cancer in 2003.

    abstract::Recent advances in molecular and cell biology have led to a greater understanding of the basic biology of bladder cancer. However, despite these advances, surgery remains a key component of modern bladder cancer treatment. Endoscopy is the mainstay of the diagnosis and treatment of superficial bladder cancer. Adjuvant...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.3.6.781

    authors: Wade M,Seigne JD

    更新日期:2003-12-01 00:00:00

  • CyberKnife robotic radiosurgery system for tumor treatment.

    abstract::Defined by its high level of accuracy and rapid radiation dose fall-off, radiosurgery has emerged as an effective radiation technique over the past few decades. Although it was once limited to conditions of the brain, head and neck regions, technological advances in computing and imaging have allowed the application o...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.7.11.1507

    authors: Hara W,Soltys SG,Gibbs IC

    更新日期:2007-11-01 00:00:00

  • Chemoprevention of prostate cancer.

    abstract::Dietary factors and other naturally occurring substances may emerge as potent therapeutic or preventative agents in the battle against prostate cancer. Much of the current support for these agents is epidemiologically based, but new prospective studies are now underway which may support their use in conventional medic...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.3.2.203

    authors: Ward JF,Blute ML

    更新日期:2003-04-01 00:00:00

  • The influence of pH and hypoxia on tumor metastasis.

    abstract::Rapid malignant proliferation, prior to effective tumor neoangiogenesis, creates a microenvironment around solid cancers, which is predominantly hypoxic and characterized by a high interstitial fluid pressure. Presumably as an adaptive response, tumor cells favor metabolic activity with apparently inefficient energy o...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.2013.843455

    authors: Abaza M,Luqmani YA

    更新日期:2013-10-01 00:00:00

  • Advances in the management of testicular cancer.

    abstract::Although testicular cancer is currently a rare disease, the incidence is rising. The most important risk factor remains cryptorchism and there is a variable association with testicular microlithiasis. Serum tumor markers remain important for diagnosis, and they have prognostic value and can be used to monitor therapy ...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.4.4.669

    authors: Balk C,Witjes JA

    更新日期:2004-08-01 00:00:00

  • Reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia.

    abstract::Acute myeloid leukemia (AML) is a hematologic malignancy with a peak incidence over the age of 55 years. AML of older patients is less curable with conventional chemotherapy, and, when it relapses, is almost uniformly fatal. Novel treatments hold the promise of improving the results of therapy, but have failed so far ...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.8.5.785

    authors: Lekakis L,de Lima M

    更新日期:2008-05-01 00:00:00

  • Role of chemotherapy in the management of soft tissue sarcomas.

    abstract::Soft tissue sarcomas are a diverse group of rare tumors that comprise 1% of all cancers. Few randomized trials of chemotherapy have been performed but there is a clear role for agents such as doxorubicin and ifosfamide in the palliation of advanced disease. There is uncertainty as to whether sequential single-agent tr...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/era.09.176

    authors: Krikelis D,Judson I

    更新日期:2010-02-01 00:00:00

  • Finding needles in a haystack: annual low-dose computed tomography screening reduces lung cancer mortality in a high-risk group.

    abstract::Lung cancer is a global health issue. Compared with other common malignancies, the prognosis is poor as many patients present with advanced disease. The National Lung Screening Trial (NLST) aimed to identify and treat early lung cancers using annual low-dose computed tomography (CT) screening in a high-risk group. Whe...

    journal_title:Expert review of anticancer therapy

    pub_type: 评论,杂志文章

    doi:10.1586/era.11.185

    authors: Duke SL,Eisen T

    更新日期:2011-12-01 00:00:00

  • Raltitrexed in mesothelioma.

    abstract::Raltitrexed is a cytotoxic agent, rationally designed to inhibit a specific molecular target, thymidylate synthase. In contrast to other agents, raltitrexed inhibits thymidylate synthase directly and specifically in a mixed, noncompetitive manner, which may lead to an improved toxicity profile. After promising Phase I...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/era.11.136

    authors: Surmont VF,van Meerbeeck JP

    更新日期:2011-10-01 00:00:00

  • Immunotherapy for renal cell cancer in the era of targeted therapy.

    abstract::Until recently, cytokine therapy has been the only validated option for patients with advanced renal cancer. IFN-alpha is one of very few treatments that have demonstrated improved median survival compared with the appropriate control. In patients with synchronous metastases at diagnosis, debulking nephrectomy prior t...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.8.6.907

    authors: Coppin C

    更新日期:2008-06-01 00:00:00

  • Clodronate in the prevention and treatment of skeletal metastasis.

    abstract::Many solid tumors, including breast and prostate cancer, metastasize to bone, thereby putting patients at high risk for developing skeletal complications including pathologic fracture, spinal cord compression and debilitating bone pain. Patients often live for many years after developing bone metastasis, a fact that h...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.5.2.221

    authors: Gulley J,Dahut WL

    更新日期:2005-04-01 00:00:00

  • Lymph node dissection for bladder cancer: the issue of extent and feasibility in the minimally invasive era.

    abstract::Lymph node dissection in bladder cancer is an integral part of radical cystectomy. It allows for accurate staging of the patient and will, therefore, serve to dictate additional treatment and add prognostic information. The issue of what is an adequate lymphadenectomy as to the extent and boundaries of the operation, ...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/era.09.147

    authors: Ghavamian R,Hakimi AA

    更新日期:2009-12-01 00:00:00

  • Latest developments in limb-salvage surgery in osteosarcoma.

    abstract::Limb-salvage surgery plays a major role in the management of patients with osteosarcoma. As prognosis improves, reconstructive options have come under greater scrutiny with regard to their durability and functionality. The advent of computer navigation-guided reconstruction is discussed in detail, along with methods b...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/era.10.225

    authors: Mangat KS,Jeys LM,Carter SR

    更新日期:2011-02-01 00:00:00

  • Promising novel therapies for relapsed and refractory testicular germ cell tumors.

    abstract:INTRODUCTION:Germ cell tumors (GCTs) are the most common solid malignancies in young men. The overall cure rate of GCT patients in metastatic stage is excellent, however; patients with relapsed or refractory disease have poor prognosis. Attempts to treat refractory disease with novel effective treatment to improve prog...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章

    doi:10.1080/14737140.2021.1838279

    authors: Kozakova K,Mego M,Cheng L,Chovanec M

    更新日期:2020-11-02 00:00:00

  • Satraplatin: an orally available platinum analog for the treatment of cancer.

    abstract::Satraplatin is a novel, orally bioavailable, platinum anticancer drug. Platinum analogs form the mainstay of treatment for a number of cancers, including lung, ovarian, colorectal and head and neck cancer. A disadvantage of the currently marketed platinum analogs is that they must all be administered via intravenous i...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.6.7.973

    authors: Choy H

    更新日期:2006-07-01 00:00:00

  • Improving the accuracy in prognosis for Burkitt lymphoma patients.

    abstract::A recent population-based study on 2000 adult patients with Burkitt lymphoma presented a novel score that takes into account age, race and clinical stage to prognosticate survival. The outcome of patients with Burkitt lymphoma has improved in the last decade, likely due to intensive chemotherapy regimens and anti-CD20...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章

    doi:10.1586/14737140.2014.866042

    authors: Castillo JJ,Nadeem O

    更新日期:2014-02-01 00:00:00

  • Cladribine in indolent non-Hodgkin's lymphoma.

    abstract::Before the advent of rationally designed targeted antineoplastic therapies, cladribine was identified as a lymphocyte-specific cytotoxic agent. Cladribine is a purine nucleoside analogue that is resistant to cellular catabolism. Through diverse mechanisms, cladribine is equally toxic to dividing and nondividing cells,...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.8.4.535

    authors: Sigal DS,Saven A

    更新日期:2008-04-01 00:00:00

  • Current, new and novel therapy for castration-resistant prostate cancer.

    abstract::Androgen deprivation therapy is the standard of care for the initial treatment of metastatic prostate cancer. However, the majority of these patients live long enough to experience disease progression despite castration. This scenario is defined as castration-resistant prostate cancer (CRPC) and has a poor outcome and...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.2013.811154

    authors: Gaya JM,Ahallal Y,Sanchez-Salas R,Barret E,Rozet F,Galiano M,Macek P,Durand M,Cerruti J,Prapotnich D,Ropert S,Bennamoun M,Cathelineau X

    更新日期:2013-07-01 00:00:00

  • On the road to treatment-free remission in chronic myeloid leukemia: what about 'the others'?

    abstract:INTRODUCTION:The treatment of chronic myeloid leukemia (CML) has been drastically changed by the approval of tyrosine kinase inhibitors (TKIs). CML is now managed as a chronic disease requiring both long-term treatment and close molecular monitoring in the majority of patients. AREAS COVERED:Evidence suggests that in ...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章

    doi:10.1080/14737140.2020.1829483

    authors: Stagno F,Breccia M,Di Raimondo F

    更新日期:2020-12-01 00:00:00

  • Adrenocortical carcinoma: role of laparoscopic surgery in treatment.

    abstract::Adrenocortical carcinoma is a rare disorder with a prevalence of one case per 1.7 million people and a generally poor prognosis. It accounts for 0.02% of all cancer cases and 0.2% of cancer deaths. Within the past three decades, accurate diagnosis, precise radiologic localization, satisfactory preoperative medical man...

    journal_title:Expert review of anticancer therapy

    pub_type: 杂志文章,评审

    doi:10.1586/14737140.7.9.1295

    authors: Haleblian GE,Wilson C,Haddad D,Albala DM

    更新日期:2007-09-01 00:00:00