Cancer therapy: know your enemy?

Westhoff, Mike-Andrew; Brühl, Oliver; Debatin, Klaus‐Michael

doi:10.1186/s40348-014-0010-2

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…Therefore, major attention was focused on the study of the role of tumor microenvironment (TME) not only in tumor initiation but also in progression and metastasis. The hypothesis of cancer cell development and proliferation only in a conducive environment has been made by Paget since 1889 [308]. While Paget suggested that the microenvironment facilitates or inhibits metastasis through growth-promoting/ inhibiting factors, recent research sustains that the tumor is directed into one or several possible molecular evolution pathways by signals originating in native and/or modified microenvironmental factors [309].…”

Section: The Roles Of Microenvironment-mediated Epigenetic Perturbatimentioning

confidence: 99%

Interplay of Epigenetics with Gynecological Cancer

Bleoţu¹,

Socolov²,

Antón³

et al. 2016

Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

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Recent data on the cell deregulation that occurs during the progression to cancer underlines the cooperation between genetic and epigenetic alterations leading to a malignant phenotype. Unlike genetic alterations, the epigenetic changes do not affect the DNA sequence of the genes, but determine the regulation of gene expression acting upon the genome. Moreover, unlike genetic changes, epigenetic ones are reversible, making them therapeutic targets in various conditions in general and in cancer disease in particular. The term epigenetics includes a series of covalent modifications that regulate the methylation pattern of DNA and posttranslational modifications of histones. Gene expression can also be regulated at the posttranscriptional level by micro-RNAs (miRNAs), a family of small noncoding RNAs that inhibit the translation of mRNA to protein. miRNAs can act as 'oncomiRs', as tumor suppressors, or both. In this chapter, we will (1) summarize the current literature on the key processes responsible for epigenetic regulation: DNA methylation, histone modifications and posttranscriptional gene regulation by miRNAs; (2) evaluate aberrant epigenetic modifications as essential players in cancer progression; (3) establish the roles of microenvironmentmediated epigenetic perturbations in the development of gynecological neoplasia; (4) evaluate epigenetic factors involved in drug resistance.

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Section: The Roles Of Microenvironment-mediated Epigenetic Perturbatimentioning

confidence: 99%

Interplay of Epigenetics with Gynecological Cancer

Bleoţu¹,

Socolov²,

Antón³

et al. 2016

Gynecologic Cancers - Basic Sciences, Clinical and Therapeutic Perspectives

View full text Add to dashboard Cite

show abstract

“…27 This approach resulted in a considerable life extension in the experimental animals compared with standard therapy andinterestingly -resulted in increasingly longer gaps between treatments as time progressed. 27 While generally speaking, a chronifying approach does not lend itself to pediatric cancers, 16 it is, however, a variant thereof that shows clinical promise in the treatment of childhood glioblastoma.…”

Section: New Therapeutic End Pointsmentioning

confidence: 99%

“…16 However, even with treatment success, long-term adverse effects and treatment-induced secondary cancers are, with extended life expectancies, also becoming increasingly a problem. 16 Recent advances in the analysis of whole cancer genomes and protein expression patterns, 17 combined with the increasing acceptance DOI: 10.17925/EOH.2014. 10.2.116 of the cancer stem cell model 18 and increasing appreciation of the tumour microenvironment, 15 have put to rest the notion of tumours as monolithic entities.…”

mentioning

confidence: 99%

Darwinian Principles in Cancer Therapy

Stroh¹,

Debatin²,

Westhoff³

2014

European Oncology &Amp; Haematology

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Our understanding of what components, cellular and extracellular, make up a tumour has greatly expanded over the recent years. This has led to new insight into the underlying mechanisms that mediate treatment failure and has also elucidated potential avenues of novel therapeutic approaches. Applying Darwinian principles to tumour heterogeneity helps to define alternative therapeutic end points, while targeting microenvironmental interactions between mutated tumour cells and their surroundings provide a genetically more stable target. Finally, we discuss the possible role of tumour-associated macrophages in future treatment options.

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Novel Approaches to Apoptosis-Inducing Therapies

Westhoff

Marschall

Debatin

2016

Apoptosis in Cancer Pathogenesis and Anti-Cancer Therapy

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Induction of apoptotic programmed cell death is one of the underlying principles of most current cancer therapies. In this review, we discuss the limitations and drawbacks of this approach and identify three distinct, but overlapping strategies to avoid these difficulties and further enhance the efficacy of apoptosis-inducing therapies. We postulate that the application of multi-targeted small molecule inhibitor cocktails will reduce the risk of the cancer cell populations developing resistance towards therapy. Following from these considerations regarding population genetics and ecology, we advocate the reconsideration of therapeutic end points to maximise the benefits, in terms of quantity and quality of life, for the patients. Finally, combining both previous points, we also suggest an altered focus on the cellular and molecular targets of therapy, i.e. targeting the (cancer cells') interaction with the tumour microenvironment.

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Cancer therapy: know your enemy?

Cited by 5 publications

References 18 publications

Interplay of Epigenetics with Gynecological Cancer

Interplay of Epigenetics with Gynecological Cancer

Darwinian Principles in Cancer Therapy

Novel Approaches to Apoptosis-Inducing Therapies

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