Targeting RAS in pediatric cancer: is it becoming a reality?

Purpose of review The current review aims to highlight the frequency of RAS mutations in pediatric leukemias and solid tumors and to propose strategies for targeting oncogenic RAS in pediatric cancers. Recent findings The three RAS genes (HRAS, NRAS, and KRAS) comprise the most frequently mutated oncogene family in human cancer. RAS mutations are commonly observed in three of the leading causes of cancer death in the United States, namely lung cancer, pancreatic cancer, and colorectal cancer. The association of RAS mutations with these aggressive malignancies inspired the creation of the National Cancer Institute RAS initiative and spurred intense efforts to develop strategies to inhibit oncogenic RAS, with much recent success. RAS mutations are frequently observed in pediatric cancers; however, recent advances in anti-RAS drug development have yet to translate into pediatric clinical trials. Summary We find that RAS is mutated in common and rare pediatric malignancies and that oncogenic RAS confers a functional dependency in these cancers. Many strategies for targeting RAS are being pursued for malignancies that primarily affect adults and there is a clear need for inclusion of pediatric patients in clinical trials of these agents.
Source: Current Opinion in Pediatrics - Category: Pediatrics Tags: HEMATOLOGY AND ONCOLOGY: Edited by Brigitte Widemann Source Type: research

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In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1+ or NKG2D+ GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
AbstractObjectivesPaeoniflorin, a representative pinane monoterpene glycoside in plants ofPaeoniaceae family, possesses promising anticancer activities on diverse tumours. This paper summarized the advance of Paeoniflorin on cancersin vivo andin vitro, discussed the related molecular mechanisms, as well as suggested some perspectives of the future investigations.Key findingsAnticancer activities of paeoniflorin have been comprehensively investigated, including liver cancer, gastric cancer, breast cancer, lung cancer, pancreatic cancer, colorectal cancer, glioma, bladder cancer and leukaemia. Furthermore, the potential mole...
Source: Journal of Pharmacy and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Review Source Type: research
ConclusionsThis targeted methylation assay detected cancer signal across>20 cancer types with a single, fixed, low false positive rate and highly accurate TOO localization. These data support the feasibility of a single test that can screen for multiple cancers.Clinical trial identificationNCT02889978, NCT03085888.Editorial acknowledgementSarah Prins, PhD (GRAIL, Inc.), and Megan P. Hall, PhD (GRAIL, Inc.).Legal entity responsible for the studyGRAIL, Inc.FundingGRAIL, Inc.DisclosureG.R. Oxnard: Advisory / Consultancy, Officer / Board of Directors: Inivata; Honoraria (self): Guardant Health; Honoraria (self): Sysmex; Hon...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research
Authors: Mendoza-Almanza G, Ortíz-Sánchez E, Rocha-Zavaleta L, Rivas-Santiago C, Esparza-Ibarra E, Olmos J Abstract Cervical cancer (CC) is one of the leading causes of cancer-associated mortalities in women from developing countries. Similar to other types of cancer, CC is considered to be a multifactorial disease, involving socioeconomic, cultural, immunological and epigenetic factors, as well as persistent human papilloma virus (HPV) infection. It has been well established that cancer stem cells (CSCs) play an important role in defining tumor size, the speed of development and the level of regressi...
Source: Oncology Letters - Category: Cancer & Oncology Tags: Oncol Lett Source Type: research
Studies have identified that the polymorphism rs10069690 of telomerase reverse transcriptase (TERT) is associated with cancer risk, but the results remain inconclusive. We performed a meta ‐analysis of 45 published studies including 329,035 cases and 730,940 controls. This meta‐analysis suggested that the TERT rs10069690 polymorphism may be a risk factor for cancer, especially breast cancer, ovarian cancer, and lung cancer. Further functional studies are warranted to reveal the ro le of the polymorphism in carcinogenesis. AbstractBackgroundStudies have identified that the telomerase reverse transcriptase (TERT) gene po...
Source: Molecular Genetics & Genomic Medicine - Category: Genetics & Stem Cells Authors: Tags: ORIGINAL ARTICLE Source Type: research
CONCLUSIONS: NPO funding by cancer type is not proportionate with individual cancer burden on society. Disease stigma negatively impacts funding. A significant need exists to increase awareness and funding for many undersupported but common and highly lethal cancers. PMID: 31319386 [PubMed - in process]
Source: Journal of the National Comprehensive Cancer Network : JNCCN - Category: Cancer & Oncology Tags: J Natl Compr Canc Netw Source Type: research
In this study, we reviewed major human studies on the health risks of radiation exposure and showed that sex-related factors may potentially influence the long-term response to radiation exposure. Available data suggest that long-term radiosensitivity in women is higher than that in men who receive a comparable dose of radiation. The report on the biological effects of ionizing radiation (BEIR VII) published in 2006 by the National Academy of Sciences, United States emphasized that women may be at significantly greater risk of suffering and dying from radiation-induced cancer than men exposed to the same dose of radiation....
Source: Frontiers in Genetics - Category: Genetics & Stem Cells Source Type: research
Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. Introduction Gallbladder cancer (GBC), the sixth most common gastrointestinal cancer, is an uncommon but challenging disease. Its incidence has recently increased highly worldwide (1). The risk factors for GBC include sex, aging, obesity, chronic cholecystitis, and cholelithiasis (2, 3). Because of the lack of an effective early diagnostic method, the disease often is not diagnosed ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions Several model systems are now available to characterize the MSC-tumour interplay in the TME. These offer early promise in establishing robust preclinical platforms for the identification of crucial molecular pathways and for the assessment of clinical efficacy of novel drugs to inhibit cancer development and progression. However, selection of the right model for a given study should be shaped on the purpose, and should also consider fixed biological, biochemical, and biophysical parameters according to the specific tumour type. Finally, in order to get reliable and useful results to be translated to the clinic...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Conclusions This review describes how leukocyte-heparanase can be a double-edged sword in tumor progression; it can enhance tumor immune surveillance and tumor cell clearance, but also promote tumor survival and growth. We also discuss the potential of using heparanase in leukocyte therapies against tumors, and the effects of heparanase inhibitors on tumor progression and immunity. We are just beginning to understand the influence of heparanase on a pro/anti-tumor immune response, and there are still many questions to answer. How do the pro/anti-tumorigenic effects of heparanase differ across different cancer types? Does...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
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