Translating RB1 Predictive Value in Clinical Cancer Therapy: Are We There Yet?

Translating RB1 Predictive Value in Clinical Cancer Therapy: Are We There Yet? Biochem Pharmacol. 2019 Jun 06;: Authors: Indovina P, Pentimalli F, Conti D, Giordano A Abstract The retinoblastoma RB1 gene has been identified in the 80s as the first tumor suppressor. RB1 loss of function, as well alterations in its pathway, occur in most human cancers and often have prognostic value. RB1 has a key role in restraining cell cycle entry and, along with its family members, regulates a myriad of cellular processes and affects cell response to a variety of stimuli, ultimately determining cell fate. Consistently, RB1 status is a crucial determinant of cell response to antitumoral therapies, impacting on the outcome of both traditional and modern anti-cancer strategies, including precision medicine approaches, such as kinase inhibitors, and immunotherapy. Despite many efforts however, the predictive value of RB1 status in the clinical practice is still underused, mainly owing to the complexity of RB1 function, to differences depending on the cellular context and on the therapeutic strategies, and, not-lastly, to technical issues. Here, we provide an overview of studies analyzing the role of RB1 in response to conventional cytotoxic and cytostatic therapeutic agents in different cancer types, including hormone dependent ones. We also review RB1 predictive value in the response to last generation CDK4/6 inhibitors, other kinase inhibitors, and immunotherapy and disc...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research

Related Links:

Conclusion: The majority of children with RB in Uganda present clinically with leucokoria, and their parents or guardians seek medical intervention at a later stage. Moreover, there was a noticeably significant lag period for the patients to begin treatment after the diagnosis was done. PMID: 31316824 [PubMed]
Source: Journal of Ophthalmology - Category: Opthalmology Tags: J Ophthalmol Source Type: research
by Hye-Yeoung Yun, Min Wook Kim, Hye Seon Lee, Wantae Kim, Ji Hye Shin, Hyunmin Kim, Ho-Chul Shin, Hwangseo Park, Byung-Ha Oh, Won Kon Kim, Kwang-Hee Bae, Sang Chul Lee, Eun-Woo Lee, Bonsu Ku, Seung Jun Kim Human papillomaviruses (HPVs) are causative agents of various diseases associated with cellular hyperproliferation, including cervical cancer, one of the most prevalent tumors in women. E7 is one of the two HPV-encoded oncoproteins and directs recruitment and subsequent degradation of tumor-suppre ssive proteins such as retinoblastoma protein (pRb) via its LxCxE motif. E7 also triggers tumorigenesis in a pRb-independen...
Source: PLoS Biology: Archived Table of Contents - Category: Biology Authors: Source Type: research
In this study, we have aimed to show and compare the antileukemic effects of aprepitant and L-733,060 on acute and chronic myeloid leukemic cells by using in-vitro experiments, such as WST-1, cell imaging, annexin-V binding, soft agar colony formation, and Hoescht staining. As a result, we have determined that both aprepitant and L-733,060 had strong antiproliferative effects on K562 and HL-60 cells. Moreover, the two drugs caused significant apoptosis and decreased colony forming depending on concentration increase. These findings suggested that NK1R antagonists exhibited antileukemic activities and may be considered to h...
Source: Anti-Cancer Drugs - Category: Cancer & Oncology Tags: Preclinical Reports Source Type: research
To evaluate the safety and efficacy of intra-arterial chemotherapy (IAC) for the primary or secondary treatment of infants diagnosed with advanced retinoblastoma before 3  months of age.
Source: BMC Cancer - Category: Cancer & Oncology Authors: Tags: Research article Source Type: research
This study assesses the central nervous system (CNS) pharmacokinetics and tumor pharmacodynamics of ribociclib, a highly selective CDK4/6-inhibitor, in patients with recurrent glioblastoma. EXPERIMENTAL DESIGN: Recurrent glioblastoma patients with intact retinoblastoma protein (RB) expression and CDKN2A deletion or CDK4/6 amplification were treated with ribociclib daily (900 mg) for 5 days before tumor resection. Blood, tumor, and cerebrospinal fluid (CSF) samples were collected and total and unbound ribociclib concentrations were determined. Pharmacodynamic effects, assessed by RB and FOXM1 phosphorylation, were comp...
Source: Clinical Cancer Research - Category: Cancer & Oncology Authors: Tags: Clin Cancer Res Source Type: research
CONCLUSIONS: Based on our results decorin may be a candidate therapeutic agent in the battle against liver cancer, but several questions need to be answered. It is certain that decorin is capable to exert its suppressor effect in hepatoma cells without respect to their phenotype and molecular background. PMID: 31271881 [PubMed - as supplied by publisher]
Source: Cellular Signalling - Category: Cytology Authors: Tags: Cell Signal Source Type: research
ConclusionsFrom our data we conclude that impairment of the cyclin D-CDK4/6-Rb pathway is a frequent feature of HCC and that it is associated with a unfavourable prognosis. We also found that ribociclib exhibits a preferential antineoplastic activity in Rb-high HCC cells. Our results warrant further investigation of Rb and p16 expression as markers of HCC sensitivity to ribociclib.
Source: Cellular Oncology - Category: Cancer & Oncology Source Type: research
In this study, we attempted to ascertain the biological role and underlying regulatory mechanism of SNHG16 in RB progression. The expression levels of SNHG16 were measured in RB tissues and cell lines. The effects of SNHG16 knockdown on the proliferation, colony formation, cell cycle progression and apoptosis were investigated using corresponding experiments. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation assay were applied to identify potential microRNAs (miRs) that could bind with SNHG16. A nude model was established to investigate the effect of SNHG16 knockdown on tumor growth in vivo. We...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
Authors: Di Sante G, Pagé J, Jiao X, Nawab O, Cristofanilli M, Skordalakes E, Pestell RG Abstract Introduction: Collaborative interactions between several diverse biological processes govern the onset and progression of breast cancer. These processes include alterations in cellular metabolism, anti-tumor immune responses, DNA damage repair, proliferation, anti-apoptotic signals, autophagy, epithelial-mesenchymal transition, components of the non-coding genome or onco-mIRs, cancer stem cells and cellular invasiveness. The last two decades have revealed that each of these processes are also directly regulated ...
Source: Expert Review of Anticancer Therapy - Category: Cancer & Oncology Tags: Expert Rev Anticancer Ther Source Type: research
In this study, we attempted to ascertain the biological role and underlying regulatory mechanism of SNHG16 in RB progression. The expression levels of SNHG16 were measured in RB tissues and cell lines. The effects of SNHG16 knockdown on the proliferation, colony formation, cell cycle progression and apoptosis were investigated using corresponding experiments. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation assay were applied to identify potential microRNAs (miRs) that could bind with SNHG16. A nude model was established to investigate the effect of SNHG16 knockdown on tumor growth in vivo. We...
Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - Category: Drugs & Pharmacology Authors: Tags: Biomed Pharmacother Source Type: research
More News: Cancer | Cancer & Oncology | Cancer Therapy | Drugs & Pharmacology | Eye Cancers | Genetics | Hormones | Immunotherapy | Retinoblastoma | Science | Study