CCR5 blockage by maraviroc: a potential therapeutic option for metastatic breast cancer

Pervaiz, Asim; Zepp, Michael; Mahmood, Saqib; Ali, Doaa M.; Berger, Martin R.; Adwan, Hassan

doi:10.1007/s13402-018-0415-3

Cited by 56 publications

(39 citation statements)

References 54 publications

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“…CCR5, one of the immune related genes upregulated in BRAFwt tumors is also upregulated in some human mammary tumors and appears to promote metastasis [61]. Antagonists of CCR5 are currently being assessed for their anti-tumor activity in aggressive tumors that express the gene [61][62][63].…”

Section: Discussionmentioning

confidence: 99%

RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors

et al. 2020

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Background: Invasive urothelial carcinoma (iUC) is highly similar between dogs and humans in terms of pathologic presentation, molecular subtypes, response to treatment and age at onset. Thus, the dog is an established and relevant model for testing and development of targeted drugs benefiting both canine and human patients. We sought to identify gene expression patterns associated with two primary types of canine iUC tumors: those that express a common somatic mutation in the BRAF gene, and those that do not. Methods: We performed RNAseq on tumor and normal tissues from pet dogs. Analysis of differential expression and clustering, and positional and individual expression was used to develop gene set enrichment profiles distinguishing iUC tumors with and without BRAFV595E mutations, as well as genomic regions harboring excessive numbers of dysregulated genes. Results: We identified two expression clusters that are defined by the presence/absence of a BRAFV595E (BRAFV600E in humans) somatic mutation. BRAFV595E tumors shared significantly more dysregulated genes than BRAF wild-type tumors, and vice versa, with 398 genes differentiating the two clusters. Key genes fall into clades of limited function: tissue development, cell cycle regulation, immune response, and membrane transport. The genomic site with highest number of dysregulated genes overall lies in a locus corresponding to human chromosome 8q24, a region frequently amplified in human urothelial cancers. Conclusions: These data identify critical sets of genes that are differently regulated in association with an activating mutation in the MAPK/ERK pathway in canine iUC tumors. The experiments also highlight the value of the canine system in identifying expression patterns associated with a common, shared cancer.

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Section: Discussionmentioning

confidence: 99%

RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors

et al. 2020

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“…Finally, recent studies have shown that CCR5 antagonists are also potent antioncogenic and antimetastatic effectors for various cancer cell lines and xenografts . CCR5 blockade results in a decreased invasion, migration, metastatic potential cell proliferation and leads to proapoptotic signaling …”

Section: Preclinical Antineoplastic Activity Of Haart Drugsmentioning

confidence: 99%

“…Finally, recent studies have shown that CCR5 antagonists are also potent antioncogenic and antimetastatic effectors for various cancer cell lines and xenografts. [174][175][176][177][178] CCR5 blockade results in a decreased invasion, migration, metastatic potential cell proliferation and leads to proapoptotic signaling. 174,176,179 Thus, the preclinical data on HAART components point to its protective effect against cancer for virtually every class of drug, which is very promising in terms of drug repositioning.…”

Section: Preclinical Antineoplastic Activity Of Haart Drugsmentioning

confidence: 99%

HIV‐1, HAART and cancer: A complex relationship

Шмакова

Germini

Vassetzky

2019

Intl Journal of Cancer

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HIV infected people are at higher risk of developing cancer, although it is globally diminished in the era of highly active antiretroviral treatment (HAART). Recently, antioncogenic properties of some HAART drugs were discovered. We discuss the role of HAART in the prevention and improvement of treatment outcomes of cancers in HIV‐infected people. We describe different trends in HAART–cancer relationships: cancer‐predisposing as well as cancer‐preventing. We cover the roles of particular drug regimens in cancer prevention. We also describe the causes of cancer treatment with HAART drugs in HIV‐negative people, including ongoing clinical studies that may directly point to a possible independent anti‐oncogenic activity of HAART drugs. We conclude that despite potent antioncogenic activities of every class of HAART drugs reported in preclinical models, the evidence to date indicates that their independent clinical impact in HIV‐infected people is limited. Improved cancer prevention strategies besides HAART are needed to reduce HIV‐cancer‐related mortality.

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“…However, recently the research involving the influence of CCR5 on different conditions has been intensified. Such studies address the CCR5 molecule per se (Castanheira et al, 2019; Jiao et al, 2018; Liu et al, 2018; Umansky, Blattner, Gebhardt, & Utikal, 2017), CCR5 pharmacological blockade (Moy et al, 2017; Pervaiz et al, 2019), CCR5 gene editing (Xie, Zhan, Ge, & Tang, 2019) and the genetic variant CCR5Δ32 (Fatima et al, 2019; Kaminski, Ellwanger, Sandrim, Pontillo, & Chies, 2019; Kletenkov et al, 2019; Słomiński et al, 2017; Toson et al, 2017; Troncoso et al, 2018). The resurgence of research involving these different aspects of CCR5 is due to two main factors: the advancement of gene‐editing technologies, which allow the exploration of the metabolic and pathophysiological effects of CCR5 editing (Allen et al, 2018; Qi et al, 2018; Vangelista & Vento, 2018; Xu et al, 2017), and the development of CCR5 blockers for clinical use (Vangelista & Vento, 2018).…”

Section: Introductionmentioning

confidence: 99%

“…On the other hand, the use of CCR5 blockers has been increasingly explored, and several studies support the use of this technology for the treatment of different diseases. For example, CCR5 blockers have a good potential for treating various types of cancer (Halama et al, 2016; Halvorsen et al, 2016; Mencarelli et al, 2013; Nishikawa et al, 2019; Pervaiz et al, 2019; Sicoli et al, 2014; Tanabe, Sasaki, Mukaida, & Baba, 2016; Velasco‐Velázquez et al, 2012), graft‐versus‐host disease (Moy et al, 2017; Reshef et al, 2019), inflammatory bowel disease (Mencarelli et al, 2016) and stroke (Joy et al, 2019). Therefore, the lack of CCR5 is deleterious in some situations, but blocking this receptor may be desirable in specific clinical contexts.…”

Section: Introductionmentioning

confidence: 99%

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

Ellwanger

Kaminski

Rodrigues

et al. 2020

Int J Immunogenetics

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The CCR5 molecule was reported in 1996 as the main HIV‐1 co‐receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV‐1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the “renaissance of CCR5 research,” this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.

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CCR5 blockage by maraviroc: a potential therapeutic option for metastatic breast cancer

Cited by 56 publications

References 54 publications

RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors

RNAseq expression patterns of canine invasive urothelial carcinoma reveal two distinct tumor clusters and shared regions of dysregulation with human bladder tumors

HIV‐1, HAART and cancer: A complex relationship

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

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