AACR Cancer Progress Report 2016

Davidson, Nancy E.; Armstrong, Scott A.; Coussens, Lisa M.; Cruz‐Correa, Marcia; DeBerardinis, Ralph J.; Doroshow, James H.; Foti, Margaret; Hwu, Patrick; Kensler, Thomas W.; Morrow, Monica; Mulligan, Charles; Pao, William; Platz, Elizabeth A.; Smith, Thomas J.; Willman, Cheryl L.

doi:10.1158/1078-0432.ccr-16-1993

Cited by 30 publications

(21 citation statements)

References 186 publications

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“…A large number of oncogenic viruses have been reported in terrestrial and aquatic wildlife and domestic animals 14,15 . Meanwhile, in humans, the number of cancer incidences identified as attributable to pathogens has tripled in only 4 years 16,17 , now accounting for 15% of all human cancers. Furthermore, emerging infectious disease events in humans are dominated by zoonoses (diseases transmitted to humans from animals, 60.3%), with the majority of these (71.8%) originating in wildlife 18–20 .…”

Section: Introductionmentioning

confidence: 99%

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

et al. 2018

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Wildlife populations are under intense anthropogenic pressures, with the geographic range of many species shrinking, dramatic reductions in population numbers and undisturbed habitats, and biodiversity loss. It is postulated that we are in the midst of a sixth (Anthropocene) mass extinction event, the first to be induced by human activity. Further, threatening vulnerable species is the increased rate of emerging diseases, another consequence of anthropogenic activities. Innovative approaches are required to help maintain healthy populations until the chronic underlying causes of these issues can be addressed. Fibropapillomatosis in sea turtles is one such wildlife disease. Here, we applied precision-medicine-based approaches to profile fibropapillomatosis tumors to better understand their biology, identify novel therapeutics, and gain insights into viral and environmental triggers for fibropapillomatosis. We show that fibropapillomatosis tumors share genetic vulnerabilities with human cancer types, revealing that they are amenable to treatment with human anti-cancer therapeutics.

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Section: Introductionmentioning

confidence: 99%

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

et al. 2018

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“…The intermittent exposure hypothesis suggests that frequent exposure of untanned skin to intense sunlight is particularly effective in increasing risk of melanoma (Elwood and Jopson, 1997). The current belief is that UVR is responsible for up to 90% of melanoma incidence in the US, with up to 8% attributed to indoor tanning (AACR, 2016). Among sun safe practices recommended to reduce melanoma risk are use of hats and clothing that cover arms and legs (AACR, 2016).…”

Section: Discussionmentioning

confidence: 99%

“…The current belief is that UVR is responsible for up to 90% of melanoma incidence in the US, with up to 8% attributed to indoor tanning (AACR, 2016). Among sun safe practices recommended to reduce melanoma risk are use of hats and clothing that cover arms and legs (AACR, 2016). Given similarities in skin pigmentation between the Iranian and European American populations analyzed in our study, lower melanoma rates in Iran in the context of standardized UVR may be partly explained by differences in clothing and coverage in the two populations.…”

Section: Discussionmentioning

confidence: 99%

Incidence of cutaneous malignant melanoma in Iranian provinces and American states matched on ultraviolet radiation exposure: an ecologic study

Moslehi

Zeinomar

Boscoe

2018

Environmental Pollution

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Objectives Ultraviolet radiation (UVR), with UVB and UVA as the relevant components, is a risk factor for melanoma. Complete ascertainment and registration of melanoma in Iran was conducted in five provinces (Ardabil, Golestan, Mazandaran, Gilan and Kerman) during 1996–2000. The aim of our study was to compare population-based incidence data from these provinces with rates in the United States (US) while standardizing ambient UVR. Methods Population-based rates representing all incident cases of melanoma (1996–2000) across the five Iranian provinces were compared to rates of melanoma among white non-Hispanics in the US. Overall age-standardized rates (ASR) for Iran and the US (per 100,000 person-years adjusted to 2000 world population) and standardized rate ratios (SRR) were calculated. We measured erythemally-weighted average solar UVR exposures (with contributions from both UVB and UVA range) of the five Iranian provinces using data from NASA's Total Ozone Mapping Spectrometer and selected five US states (Kentucky, Utah, Texas, Oklahoma, and Hawaii) with matching UVR exposure to each province. Incidence rates of melanoma during 1996–2000 in each Iranian province were compared to rates among white non-Hispanics in its UVR-matched US state. Results The overall male and female ASRs of melanoma were 0.60 (95%CI: 0.56–0.64) and 0.46 (95%CI: 0.42–0.49), respectively, for Iran and 22.78 (95%CI: 22.42–23.14) and 16.61 (95%CI: 16.30–16.92) for the US. SRRs of melanoma comparing US to Iran were 37.97 (95%CI: 35.78–40.29) for males and 36.11 (95%CI: 33.69–38.70) for females, indicating significantly higher incidence in the US. ASRs and age-specific rates of melanoma for both genders were significantly lower in each Iranian province compared to its UVR-matched US state. Conclusion The markedly lower incidence rates of melanoma in Iranian provinces with similar UVR exposures to US states underscore the need for additional comparative studies to decipher the influence of other extrinsic and intrinsic factors on the risk of this malignancy.

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“…Sea turtle fibropapillomatosis (FP) is potentially a canary in the coalmine, indicating that continued human-induced environmental damage may be an alternative route by which oncogenicity is conferred on normally well-tolerated viruses. This is particularly worrying as long-lived reptiles have normally robust anti-cancer defenses 1,2 , and as there are already a range of human viruses known to be capable of inducing tumor formation when the host immune system is compromised 3,4 . In addition to improving wildlife conservation medicine, fibropapillomatosis precision oncology can reveal the precise mechanisms through with environmental triggers, viral dynamics and host cell transformation can rapidly induce novel cancer incidence on an epidemic scale, thereby simultaneously informing human cancer research 2,5 .…”

Section: Introductionmentioning

confidence: 99%

Mutational, transcriptional and viral shedding dynamics of the marine turtle fibropapillomatosis tumor epizootic

Yetsko

Farrell

Stammnitz

et al. 2020

Preprint

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Sea turtle populations are directly and indirectly under threat from a range of anthropogenic processes. Perhaps the most visibly apparent of these is the disfiguring tumor disease epizootic (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at a number of affected sites globally. Environmental exposures seem key to inducing tumor development, possibly through weakening host immune systems to the point of enabling pathogen-induced tumor formation. However, we do not yet understand the precise molecular and mutational events driving fibropapillomatosis tumor formation and progression. Similarly, many open questions remain about the role of the herpesvirus (chelonid herpesvirus 5, ChHV5) associated with the disease as a potential co-trigger, and whether its occurrence within tumors is causative or opportunistic. Without improved understanding of the basic biology of this disease epizootic, treatment, containment and mitigation options are severely hampered.To address fundamental questions relating to the oncogenic signaling, mutational spectrum, viral load, viral transcriptional status (lytic or latent) and spread, we employed transcriptomic profiling, whole genome sequencing, immunohistochemistry and environmental (e)DNAbased monitoring of viral shedding. In particular we focused on the mutational landscape of tumors and assessing the transcriptional similarity of external (skin) and internal (visceral organs) tumors, and the oncogenic signaling events driving early stage tumor growth and post-surgical tumor regrowth. These analyses revealed that internal fibropapillomatosis tumors are molecularly distinct from the more common external tumors. However, our molecular analyses also revealed that there are a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common between internal and external tumors, such as the MAPK, Wnt, TGFβ and TNF oncogenic signaling pathways. We also determined that the tumor genomes can harbor copy number gains, indicating potentially viral-independent oncogenic processes. Genes within such mutated genomic regions have known roles in human skin cancer, including MAPK-associated genes. Turtles attempt to mount an immune response, but in some animals this appears to be insufficient to prevent tumor development and growth. ChHV5 was transcriptionally latent in all tumor stages sequenced, including early stage and recurrent tumors. We also revealed that the tumors themselves are the primary source of viral shedding into the marine environment and, if they are surgically removed, the level of ChHV5 in the water column drops.Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, therapeutic treatment, and appropriate quarantine responses for this wildlife epizootic. Furthermore, they provide insights into human pathogen-induced cancers, particularly mechanisms which are difficult to s...

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AACR Cancer Progress Report 2016

Cited by 30 publications

References 186 publications

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

Sea turtle fibropapilloma tumors share genomic drivers and therapeutic vulnerabilities with human cancers

Incidence of cutaneous malignant melanoma in Iranian provinces and American states matched on ultraviolet radiation exposure: an ecologic study

Mutational, transcriptional and viral shedding dynamics of the marine turtle fibropapillomatosis tumor epizootic

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