Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back

Yadav, Ankita; Srikrishna, Saripella; Gupta, Subash C.

doi:10.1016/j.tips.2016.05.010

Cited by 59 publications

(59 citation statements)

References 116 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the last years, Drosophila has proven useful in establishing genetic models of human diseases due to its intrinsic features as the low cost of maintenance, the reduced genetic redundancy, the high conservation of human signalling pathways and disease genes and the ease of mutant flies generation. The fact that Drosophila contains functional homologs for the 68% of human cancer-related genes, including the proto-oncogene RET, has provided a rationale for using this model in tumour pathogenesis studies and in anti-cancer drug discovery (Yadav et al 2016). In this frame, Drosophila has been used to study MEN2 syndrome by the generation of transgenic flies that expressed mutated forms of Drosophila RET (dRet) in the developing retina, a neuroepithelial tissue that shows remarkable evolutionary conservation of receptor tyrosine kinase signal transduction pathways.…”

Section: Drosophila Cancer Modelmentioning

confidence: 99%

“…In conclusion, Drosophila offers powerful tools to investigate the molecular basis of MTC and to perform high-throughput screening of novel cancer drugs, as well as to test multi-targeted agents and combination therapy (Dar et al 2012, Das et al 2014, Yadav et al 2016. However, the employment of Drosophila for studies on MTC has several limitations that need to be considered.…”

Section: Drosophila Cancer Modelmentioning

confidence: 99%

“…Nonetheless, the study of tumour progression, which may rely on tissuespecific conditions, may be compromised by the lack of thyroid and C cells-like structures (Das & Cagan 2010). Moreover, given that the anatomy and physiology of flies are significantly different from those of mammals, it will be important to clarify some issues related to the potential efficacy in humans of drugs that have been tested in Drosophila (Yadav et al 2016).…”

Section: Drosophila Cancer Modelmentioning

confidence: 99%

See 2 more Smart Citations

Animal models of medullary thyroid cancer: state of the art and view to the future

Mantovani

Gaudenzi

Circelli

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

Medullary thyroid carcinoma is a neuroendocrine tumour originating from parafollicular C cells accounting for 5-10% of thyroid cancers. Increased understanding of diseasespecific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid carcinoma. These drugs increase progression-free survival; however, they are often poorly tolerated and most treatment responses are transient. Animal models are indispensable tools for investigating the pathogenesis, mechanisms for tumour invasion and metastasis and new therapeutic approaches for cancer. Unfortunately, only few models are available for medullary thyroid carcinoma. This review provides an overview of the state of the art of animal models in medullary thyroid carcinoma and highlights future developments in this field, with the aim of addressing salient features and clinical relevance. 24:1

show abstract

Section: Drosophila Cancer Modelmentioning

confidence: 99%

Section: Drosophila Cancer Modelmentioning

confidence: 99%

Section: Drosophila Cancer Modelmentioning

confidence: 99%

See 1 more Smart Citation

Animal models of medullary thyroid cancer: state of the art and view to the future

Mantovani

Gaudenzi

Circelli

et al. 2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

show abstract

“…These systems enable the study of chemotherapeutic effects because xenobiotic-response pathways are highly conserved between invertebrates and humans [15], including cytochrome P450s [16,17], UDP-glucuronosyltransferases [2], and ABC transporters [18]. Similarly, numerous additional examples of responses to cytotoxic chemotherapeutics conserved between D. melanogaster and humans are known [21]. Additionally, the utility of C. elegans and D. melanogaster can be extended to chemotherapeutics that target cell proliferation pathways often constitutively activated in human cancers [22].…”

Section: Chemotherapeutic Drug Responses Are Conserved In Invertebratmentioning

confidence: 99%

Natural diversity facilitates the discovery of conserved chemotherapeutic response mechanisms

Zdraljevic

Andersen

2017

Current Opinion in Genetics & Development

View full text Add to dashboard Cite

Organismal fitness depends on adaptation to complex niches where chemical compounds and pathogens are omnipresent. These stresses can lead to the fixation of alleles in both xenobiotic responses and proliferative signaling pathways that promote survival in these niches. However, both xenobiotic responses and proliferative pathways vary within and among species. For example, genetic differences can accumulate within populations because xenobiotic exposures are not constant and selection is variable. Additionally, neutral genetic variation can accumulate in conserved proliferative pathway genes because these systems are robust to genetic perturbations given their essential roles in normal cell-fate specification. For these reasons, sensitizing mutations or chemical perturbations can disrupt pathways and reveal cryptic variation. With this fundamental view of how organisms respond to cytotoxic compounds and cryptic variation in conserved signaling pathways, it is not surprising that human patients have highly variable responses to chemotherapeutic compounds and to the activities of proliferative pathways. These different patient responses result in the low FDA-approval rates for chemotherapeutics and underscore the need for new approaches to understand these diseases and therapeutic interventions. Model organisms, especially the classic invertebrate systems of Caenorhabditis elegans and Drosophila melanogaster, can be used to combine studies of natural variation across populations with responses to both xenobiotic compounds and chemotherapeutics targeted to conserved proliferative signaling pathways.

show abstract

“…In fact, several compounds targeting cell cycle-related molecules are being tested in various phases of clinical trials, some have even received the Food and Drug Administration (FDA) approval. 22 Histone deacetylase inhibitors (HDACis) are a new class of anti-cancer agents. 23 In addition to their wellestablished effects on histone tail modifications and chromatin configuration, HDACis also regulate acetylation of non-histone proteins, 24 thus exerting broad gene regulatory effects.…”

Section: Introductionmentioning

confidence: 99%

Rescue of cell cycle progression in BRAF^V600E inhibitor–resistant human melanoma by a chromatin modifier

2017

View full text Add to dashboard Cite

The BRAF V600E -specific inhibitor vemurafenib blocks mitogen-activated protein kinase pathway and induces cell cycle arrest at G0/G1 phase leading to apoptosis of melanomas. To gain an understanding of the dynamics of cell cycle regulation during vemurafenib therapy, we analyzed several vemurafenib-resistant human melanoma sublines derived from BRAF V600E harboring vemurafenib-sensitive parental lines. Vemurafenib provoked G0/G1 phase arrest in parental but not in vemurafenib-resistant sublines. We hypothesized that refractoriness of vemurafenib-resistant sublines to vemurafenib-mediated cell cycle inhibition can be partially rescued by the chromatin modifier suberoylanilide hydroxamic acid. Suberoylanilide hydroxamic acid promoted G2/M arrest at expense of S phase irrespective of vemurafenib sensitivity. In parental lines, combination of suberoylanilide hydroxamic acid and vemurafenib induced both G0/G1 arrest and apoptosis, whereas in vemurafenib-resistant sublines combination induced G0/G1 as well as G2/M arrest resulting in dramatic cytostasis. Vemurafenib-resistant sublines exhibited extracellular signal-regulated protein kinases 1 and 2 but not AKT and hyperphosphorylation. Gene expression profiling revealed mitogen-activated protein kinase hyperactivation and deregulations of cyclins and cyclin-dependent kinases in vemurafenib-resistant sublines, all of which were reversed by suberoylanilide hydroxamic acid; changes that may explain the cytostatic effects of suberoylanilide hydroxamic acid. These results suggest that unresponsiveness of vemurafenib-resistant sublines to the biological effects of vemurafenib may be amenable by suberoylanilide hydroxamic acid. These in vitro results, while require further investigation, may provide rational biological basis for combination therapy in the management of vemurafenib-resistant melanoma.

show abstract

Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back

Cited by 59 publications

References 116 publications

Animal models of medullary thyroid cancer: state of the art and view to the future

Animal models of medullary thyroid cancer: state of the art and view to the future

Natural diversity facilitates the discovery of conserved chemotherapeutic response mechanisms

Rescue of cell cycle progression in BRAF^V600E inhibitor–resistant human melanoma by a chromatin modifier

Contact Info

Product

Resources

About

Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back

Cited by 59 publications

References 116 publications

Animal models of medullary thyroid cancer: state of the art and view to the future

Animal models of medullary thyroid cancer: state of the art and view to the future

Natural diversity facilitates the discovery of conserved chemotherapeutic response mechanisms

Rescue of cell cycle progression in BRAFV600E inhibitor–resistant human melanoma by a chromatin modifier

Contact Info

Product

Resources

About

Rescue of cell cycle progression in BRAF^V600E inhibitor–resistant human melanoma by a chromatin modifier