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Query: UNIPROT:P04637 (p53)
 77,613 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This review provides a summary of the European Association for Cancer Research Award Lecture, presented at the ECCO12 meeting in Copenhagen in September 2003. It describes what we have learnt about the mechanisms responsible for deregulating RNA polymerase III transcription in transformed cells. A network has been discovered of unanticipated links to key tumour suppressors and oncogenes. Novel functions have been revealed for RB, p53 and c-Myc, that may help explain their profound biological effects.
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PMID:RNA polymerase III transcription--a battleground for tumour suppressors and oncogenes. 1468 85

This review provides a summary of the European Association for Cancer Research 'Cancer Researcher Award' lecture which was presented at the EACR21 meeting in Oslo, Norway, in July 2010. The review focuses on the importance of programmed cell death regulation in tumour development and cancer therapy. Eradication of damaged cells is a principal mechanism of protection against cancer and involves key tumour suppressor proteins such as p53. Cell death-associated tumour suppressors, including p53, are often inactivated during the genesis of cancer and this poses problems for many forms of therapy which require these death proteins for a therapeutic response. The identification therefore of other factors and pathways that regulate cell viability is of prime importance for the development of rationalised new strategies to invoke tumour cell death. Historically, studies of programmed cell death in cancer have focused on the evolutionarily conserved process of apoptosis. More recently, however, attention has also turned to another process termed 'autophagy' which has profound effects on cell viability. Principally, autophagy serves to traffic damaged proteins and organelles to the lysosome for degradation. It functions therefore as a homeostatic mechanism that impinges on both protein and genome integrity. Summarized here are our findings linking p53 to autophagy and how this led to the identification of the human Damage-Regulated Autophagy Modulator (DRAM) family. Further discussion relates to our subsequent studies, together with those of others, that have yielded insights into the selective targeting of autophagy for the treatment of malignant disease.
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PMID:p53 and autophagy in cancer: guardian of the genome meets guardian of the proteome. 2111 7

The 15th St Gallen International Breast Cancer Conference was held in Vienna for the second time, from 15th-18th March 2017. 4000 people from 105 countries all over the world were invited to take part in the event. The real highlight of the conference was the last day with the International Consensus Session which was chaired by around 50 experts on breast cancer worldwide. With reference to data from scientific research, the consensus panel tried to offer guidelines for the management of breast cancer with the aim of providing patients with optimal treatment. The topics covered focused on the treatment of breast cancer, consideration of surgery, radiotherapy, neo-adjuvant, and adjuvant systemic therapy for breast cancer, as well as genetics and prevention of breast cancer. In particular, in terms of precision medicine, an important topic of the conference was 'is it possible to think that it could become routine in clinical practice to use immunotherapy and targeted therapy based on genetic signatures?' In view of personalised therapy, it is important to take into consideration women's treatment preferences. It is also important not only to offer guidelines which help breast cancer experts all over the world to choose the proper treatment for women with breast cancer but also to discuss the pros and cons of the therapy with the patient. This allows for a better understanding of the disease. 'From the maximum tolerable to the minimum effective treatment: it is essential to escalate treatment when necessary and to de-escalate when unnecessary'. These few words could summarise the meaning of the 15th St Gallen International Breast Cancer Conference. Prof Martine Piccart-Gebhart was awarded with the St Gallen International Breast Cancer Award 2017 for her fundamental clinical research contribution and Prof Giuseppe Curigliano with the Umberto Veronesi Memorial Award which aims to recognise a physician's leading role in advancing the science and care of breast cancer patients. Curigliano, in his lecture, spoke about the revolutionary immunotherapy in the clinical management of breast cancer (BC). For the development of these therapies, it is necessary to identify the genetic determinants of BC immune phenotypes in which The Cancer Genome Atlas (TCGA) has contributed towards this. For example, the T helper (Th-1) phenotype (ICR4), which also exhibits upregulation of immune-regulatory transcripts (eg. PDL1, PD1, FOXP3, IDO1, and CTLA4), was associated with prolonged patients' survival. Chromosome segment 4q21, which includes genes encoding the Th-1 chemokines CXCL9-11, was significantly amplified only in the immune favourable phenotype (ICR4). The mutation and neo-antigen load progressively decreased from ICR4 to ICR1 but could not explain immune phenotypic differences. Mutations of TP53 were enriched in the immune favourable phenotype (ICR4). Instead, the presence of MAP3K1 and MAP2K4 mutations were closely associated with an immune unfavourable phenotype (ICR1). Using both the TCGA and the validation dataset, the degree of MAPK deregulation segregates BC according to their immune disposition. These findings suggest that mutational-driven deregulation of MAPK pathways is linked to the negative regulation of intratumoural immune response in BC. The main themes of this congress were: 1) Surgery of the primary tumour and margins; 2) Surgery of the axilla; 3) Radiotherapy: hypofractionated, 'boost' to tumour bed, partial breast, regional node, after mastectomy, advanced technology; 4) Pathology: subtypes, TILs; 5) Multi-gene signatures and therapy; 6) Endocrine therapy: pre- and post-menopausal and duration; 7) Chemotherapy: subtypes, stages; 8) Anti-HER-2 therapy; 9) Neo-adjuvant therapy; 10) Adjuvant bisphosponates; 11) Adjuvant diet and exercise.
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PMID:Highlights from the 15th St Gallen International Breast Cancer Conference 15-18 March, 2017, Vienna: tailored treatments for patients with early breast cancer. 2849 Nov 35