How elephants beat cancer

Gaughran, Stephen J.; Pless, Evlyn; Stearns, Stephen C.

doi:10.7554/elife.21864

Cited by 17 publications

(12 citation statements)

References 7 publications

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“…Therefore, in evolution, larger animals have mechanisms to suppress cancer by either eliminating certain proto-oncogenes or duplicating tumor suppressor genes [358,359,360]. Elephants appear to have low cancer occurrence rates since they have re-functionalized the leukemia inhibitory factor pseudogene 6 (LIF6) with pro-apoptotic functions [361]. In addition, the duplication/multiplication of tumor-suppressor protein TP53 seems to provide another explanation, even though most are processed pseudogenes [362].…”

Section: Discussionmentioning

confidence: 99%

Transcription Factors That Govern Development and Disease: An Achilles Heel in Cancer

Huilgol

Venkataramani

Nandi

et al. 2019

Genes

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Development requires the careful orchestration of several biological events in order to create any structure and, eventually, to build an entire organism. On the other hand, the fate transformation of terminally differentiated cells is a consequence of erroneous development, and ultimately leads to cancer. In this review, we elaborate how development and cancer share several biological processes, including molecular controls. Transcription factors (TF) are at the helm of both these processes, among many others, and are evolutionarily conserved, ranging from yeast to humans. Here, we discuss four families of TFs that play a pivotal role and have been studied extensively in both embryonic development and cancer—high mobility group box (HMG), GATA, paired box (PAX) and basic helix-loop-helix (bHLH) in the context of their role in development, cancer, and their conservation across several species. Finally, we review TFs as possible therapeutic targets for cancer and reflect on the importance of natural resistance against cancer in certain organisms, yielding knowledge regarding TF function and cancer biology.

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Section: Discussionmentioning

confidence: 99%

Transcription Factors That Govern Development and Disease: An Achilles Heel in Cancer

Huilgol

Venkataramani

Nandi

et al. 2019

Genes

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“…Recent findings point to increased copy numbers of specific genes that may reduce cancer risk in the elephant and the bowhead whale. In the African and Asian elephants, increased copies of TP53-related sequences (p53) have been detected by genome-wide DNA sequencing [ 98 ], and some of these sequences produce functional proteins [ 99 ]. Thus, the elephant's resistance to cancer may be in part due to extra copies of a powerful tumour suppressor gene [ 100 ].…”

Section: The Cancer/degenerative-disease Trade-offmentioning

confidence: 99%

Reflections on telomere dynamics and ageing-related diseases in humans

Aviv

Shay

2018

Phil. Trans. R. Soc. B

144

113

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Epidemiological studies have principally relied on measurements of telomere length (TL) in leucocytes, which reflects TL in other somatic cells. Leucocyte TL (LTL) displays vast variation across individuals—a phenomenon already observed in newborns. It is highly heritable, longer in females than males and in individuals of African ancestry than European ancestry. LTL is also longer in offspring conceived by older men. The traditional view regards LTL as a passive biomarker of human ageing. However, new evidence suggests that a dynamic interplay between selective evolutionary forces and TL might result in trade-offs for specific health outcomes. From a biological perspective, an active role of TL in ageing-related human diseases could occur because short telomeres increase the risk of a category of diseases related to restricted cell proliferation and tissue degeneration, including cardiovascular disease, whereas long telomeres increase the risk of another category of diseases related to increased proliferative growth, including major cancers. To understand the role of telomere biology in ageing-related diseases, it is essential to expand telomere research to newborns and children and seek further insight into the underlying causes of the variation in TL due to ancestry and geographical location.This article is part of the theme issue ‘Understanding diversity in telomere dynamics’.

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“…However, not all these changes are related with the development of cancer. Those somatic genomic alterations that are actually involved in carcinogenesis are known as "driver" alterations, whereas those that are not, are called "passenger" alterations (46,47) (Figure 2).…”

Section: Somatic Alterations In Cancer Genomementioning

confidence: 99%

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

et al. 2017

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Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC. Thus, current classification differentiates between preinvasive lesions (atypical adenomatous hyperplasia and in situ ADC), minimally invasive ADC (MIA) and invasive ADC. 'Field cancerization' is a concept that refers to progressive loco-regional changes occurring in tissues exposed to carcinogens, due to the interaction of the latter with a predisposing genetic background and an appropriate tissue microenvironment. Somatic genetic alterations, including mutations but also other changes, are necessary for oncogenesis, being especially frequent in lung ADC. Changes in the epidermal growth factor receptor () gene, Kirsten rat sarcoma viral oncogene (), v-Raf murine sarcoma viral oncogene homolog B (), gene encoding neurofibromin (), anaplastic lymphoma kinase () and are the main genes that suffer alterations in the tumors of patients with ADC. Molecular profiling of these tumors allows more targeted treatments through two distinct strategies, genome-guided therapy and immunotherapy. The former, targets the aberrant pathways secondary to the genomic alteration, whereas the latter may be based on the administration of antibodies [such as those against cytotoxic T-lymphocyte antigen 4 (CTLA-4) or the programmed cell death ligand 1/protein 1 pathway (PD-L1/PD-1)] or the stimulation of the patient's own immune system to produce a specific response. These strategies are obtaining better results in selected ADC patients.

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How elephants beat cancer

Abstract: Elephants have significantly reduced their risk of cancer by duplicating an important gene called TP53.

Cited by 17 publications

References 7 publications

Transcription Factors That Govern Development and Disease: An Achilles Heel in Cancer

Transcription Factors That Govern Development and Disease: An Achilles Heel in Cancer

Reflections on telomere dynamics and ageing-related diseases in humans

Lung adenocarcinoma: from molecular basis to genome-guided therapy and immunotherapy

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