The efficacy of HRAS and CDK4/6 inhibitors in anaplastic thyroid cancer cell lines

Lopes-Ventura, S.; Pojo, Marta; Matias, Ana T.; Moura, M. M.; Marques, Inês J.; Leite, Valeriano; Cavaco, Branca

doi:10.1007/s40618-018-0947-4

Cited by 21 publications

(15 citation statements)

References 42 publications

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“…Moreover, the treatment of thyroid cancer cells with the CDK4/6 inhibitor palbociclib (PD-0332991) induces a consistent antiproliferative effect [76]. In keeping with our results, other groups have confirmed the efficacy of palbociclib in in vitro and in vivo preclinical models of TC, also in combination with a PI3K/mTOR inhibitor to bypass mechanisms of therapy resistance [89][90][91]. On the whole, we are confident that the evidence that cyclin D1 represents TC cell vulnerability may prompt preclinical and clinical studies employing CDK4/6 inhibitors for treatment of TC.…”

Section: Validation Of Noa Targetssupporting

confidence: 86%

Targeting Non-Oncogene Addiction: Focus on Thyroid Cancer

Anania

Marco

Mazzoni

et al. 2020

Cancers

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Thyroid carcinoma (TC) is the most common malignancy of endocrine organs with an increasing incidence in industrialized countries. The majority of TC are characterized by a good prognosis, even though cases with aggressive forms not cured by standard therapies are also present. Moreover, target therapies have led to low rates of partial response and prompted the emergence of resistance, indicating that new therapies are needed. In this review, we summarize current literature about the non-oncogene addiction (NOA) concept, which indicates that cancer cells, at variance with normal cells, rely on the activity of genes, usually not mutated or aberrantly expressed, essential for coping with the transformed phenotype. We highlight the potential of non-oncogenes as a point of intervention for cancer therapy in general, and present evidence for new putative non-oncogenes that are essential for TC survival and that may constitute attractive new therapeutic targets.

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Section: Validation Of Noa Targetssupporting

confidence: 86%

Targeting Non-Oncogene Addiction: Focus on Thyroid Cancer

Anania

Marco

Mazzoni

et al. 2020

Cancers

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“…Furthermore, the identification of cell cycle gene alterations, such as CCNE1 amplifications, suggest that CDK inhibitors (such as CDK4/6 inhibitors) may be a viable treatment option. Preclinical studies in ATC cell lines and ATC xenograft models further support this [71,72,73]. These findings remain to be extended to clinical trials.…”

Section: Discussionmentioning

confidence: 65%

A Systematic Review of Phase II Targeted Therapy Clinical Trials in Anaplastic Thyroid Cancer

Ljubas

Ovesen

Rusan

2019

Cancers

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Anaplastic thyroid carcinoma (ATC) is a rare, but devastating disease. Despite multimodal approaches combining surgery, chemotherapy and radiation therapy, ATC is associated with a dire prognosis, with a median overall survival of only three to ten months. Novel treatments are thus urgently needed. Recent efforts towards the characterization of the molecular landscape of ATC have led to the identification of pro-oncogenic targetable alterations, lending promise for novel targeted therapeutic approaches. This systematic review summarizes the results of phase II clinical trials of targeted therapy in ATC, providing an overview of efficacy and safety profiles. The majority of trials to date have consisted of small single-arm studies and have presented modest results. However, only a minority of trials have selected or stratified patients by molecular alterations. In the setting of BRAF V600E mutated ATC, dabrafenib/trametinib combination therapy and vemurafenib monotherapy have both demonstrated efficacy. Everolimus has furthermore shown promising results in patients with PI3K/mTOR/AKT pathway alterations. These studies underscore the importance of molecular profiling of tumors for appropriate patient selection and determination of genomic correlates of response. Clinical trials are underway testing additional targeted therapies as monotherapy, or as a part of multimodal treatment, and in combination with immunotherapy.

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“…A trial underway showed a 20% improvement in tumour size with use of a new NTRK inhibitor entrectinib. Tipifarnib ( HRAS inhibitor) and palbociclib (cyclin D-cyclin-dependent kinase 4/6 inhibitor), both also currently being investigated, have shown reduction in tumour size [ 163 ]. Further development in targeted therapy for ATCs is required.…”

Section: Tumour Microenvironment and Programmed Cell Death 1 Ligand 1 (Pd-l1) Expressionmentioning

confidence: 99%

The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy

Singh

Ham

et al. 2021

Cells

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Thyroid cancer is the most prevalent endocrine malignancy that comprises mostly indolent differentiated cancers (DTCs) and less frequently aggressive poorly differentiated (PDTC) or anaplastic cancers (ATCs) with high mortality. Utilisation of next-generation sequencing (NGS) and advanced sequencing data analysis can aid in understanding the multi-step progression model in the development of thyroid cancers and their metastatic potential at a molecular level, promoting a targeted approach to further research and development of targeted treatment options including immunotherapy, especially for the aggressive variants. Tumour initiation and progression in thyroid cancer occurs through constitutional activation of the mitogen-activated protein kinase (MAPK) pathway through mutations in BRAF, RAS, mutations in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and/or receptor tyrosine kinase fusions/translocations, and other genetic aberrations acquired in a stepwise manner. This review provides a summary of the recent genetic aberrations implicated in the development and progression of thyroid cancer and implications for immunotherapy.

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The efficacy of HRAS and CDK4/6 inhibitors in anaplastic thyroid cancer cell lines

Abstract: This study suggests that TIP and PD, which are currently in clinical trials for other types of cancer, may play a relevant role in ATC treatment, depending on the specific tumour molecular profile.

Cited by 21 publications

References 42 publications

Targeting Non-Oncogene Addiction: Focus on Thyroid Cancer

Targeting Non-Oncogene Addiction: Focus on Thyroid Cancer

A Systematic Review of Phase II Targeted Therapy Clinical Trials in Anaplastic Thyroid Cancer

The Genomic Landscape of Thyroid Cancer Tumourigenesis and Implications for Immunotherapy

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