Biological sex shapes tumour evolution across cancer types

Nature ◽  
2019 ◽  
Author(s):  
Heidi Ledford
Keyword(s):  
2019 ◽  
Author(s):  
Martin Lotz ◽  
Simon J. Furney ◽  
Amaya Virós

AbstractMany cancer types display sex and age disparity in incidence and outcome. Here, we establish a mathematical approach using cancer mutational data to analyze how sex and age shape the tumour genome. We model how age-related (clock-like) somatic mutations that arise during cell division, and extrinsic (environmental) mutations accumulate in cancer genomes. As a proof-of-concept, we apply our approach to melanoma, a cancer driven by cell-intrinsic age-related mutations and extrinsic ultraviolet light-induced mutations, and show these mutation types differ in magnitude, chronology and by sex in the distinct molecular melanoma subtypes.Our model confirms age and sex are determinants of cellular mutation rate, shaping the final mutation composition. We show mathematically for the first time how, similar to non-cancer tissues, melanoma genomes reflect a decline in cell division during ageing. We find clock-like mutations strongly correlate with the acquisition of ultraviolet light-induced mutations, but critically, males present a higher number and rate of cell division-linked mutations. These data indicate the contribution of environmental damage to melanoma likely extends beyond genetic damage to affect cell division.


Author(s):  
K. . Togawa

Agricultural workers can be exposed to a wide variety of agents (e.g. pesticides), some of which may have adverse health effects, such as cancer. To study the health effects of agricultural exposures, an international consortium of agricultural cohort studies, AGRICOH, was established. The present analysis compared cancer incidence between the AGRICOH cohorts and the general population and found lower overall cancer incidence in the AGRICOH cohorts, with some variation across cohorts for specific cancer types. The observed lower cancer incidence may be due to healthy worker bias or lower prevalence of risk factors in the agricultural populations. Further analysis is underway.


2018 ◽  
Author(s):  
Leif Ekblad

Gender identities that differ from biological sex (non-cisgender identities) appear to be more common in autism and neurodiversity. The study found that part of the non-cisgender identities could be related to having behavioral preferences of the opposite sex, but this failed to explain the higher prevalence in neurodiversity. Non-cisgender identities in neurodiversity could better be explained by having neurodiverse relationship preferences or lacking typical relationship preferences. Being part of the LGBT (Lesbian Gay Bi Transgender) community biased answers to questions about gender identity. Neurodiverse non-cisgender people, just like neurodiverse asexual people, might be better off with new communities that focus on the more relevant relationship preference differences rather than on narrow and indirect gender and sexual issues.


2019 ◽  
pp. 1-4
Author(s):  
Tikam Chand ◽  
Tikam Chand

Having role in gene regulation and silencing, miRNAs have been implicated in development and progression of a number of diseases, including cancer. Herein, I present potential miRNAs associated with BAP1 gene identified using in-silico tools such as TargetScan and Exiqon miRNA Target Prediction. I identified fifteen highly conserved miRNA (hsa-miR-423-5p, hsa-miR-3184-5p, hsa-miR-4319, hsa-miR125b-5p, hsa-miR-125a-5p, hsa-miR-6893-3p, hsa-miR-200b-3p, hsa-miR-200c-3p, hsa-miR-505-3p.1, hsa-miR-429, hsa-miR-370-3p, hsa-miR-125a-5p, hsa-miR-141-3p, hsa-miR-200a-3p, and hsa-miR-429) associated with BAP1 gene. We also predicted the differential regulation of these twelve miRNAs in different cancer types.


2019 ◽  
Vol 26 (17) ◽  
pp. 3009-3025 ◽  
Author(s):  
Bin Li ◽  
Ho Lam Chan ◽  
Pingping Chen

Cancer is one of the most deadly diseases in the modern world. The last decade has witnessed dramatic advances in cancer treatment through immunotherapy. One extremely promising means to achieve anti-cancer immunity is to block the immune checkpoint pathways – mechanisms adopted by cancer cells to disguise themselves as regular components of the human body. Many review articles have described a variety of agents that are currently under extensive clinical evaluation. However, while checkpoint blockade is universally effective against a broad spectrum of cancer types and is mostly unrestricted by the mutation status of certain genes, only a minority of patients achieve a complete response. In this review, we summarize the basic principles of immune checkpoint inhibitors in both antibody and smallmolecule forms and also discuss potential mechanisms of resistance, which may shed light on further investigation to achieve higher clinical efficacy for these inhibitors.


2020 ◽  
Vol 26 ◽  
Author(s):  
Maryam Dashtiahangar ◽  
Leila Rahbarnia ◽  
Safar Farajnia ◽  
Arash Salmaninejad ◽  
Arezoo Gowhari Shabgah ◽  
...  

: The development of recombinant immunotoxins (RITs) as a novel therapeutic strategy has made a revolution in the treatment of cancer. RITs are resulting from the fusion of antibodies to toxin proteins for targeting and eliminating cancerous cells by inhibiting protein synthesis. Despite indisputable outcomes of RITs regarding inhibiting multiple cancer types, high immunogenicity has been known as the main obstacle in the clinical use of RITs. Various strategies have been proposed to overcome these limitations, including immunosuppressive therapy, humanization of the antibody fragment moiety, generation of immunotoxins originated from endogenous human cytotoxic enzymes, and modification of the toxin moiety to escape the immune system. This paper devoted to reviewing recent advances in the design of immunotoxins with lower immunogenicity.


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