Aging and cancer最新文献

{"title":"DNA damage response inhibition-based combination therapies in cancer treatment: Recent advances and future directions","authors":"Tianen Chen,&nbsp;Suparat Tongpeng,&nbsp;Ziyi Lu,&nbsp;Win Topatana,&nbsp;Sarun Juengpanich,&nbsp;Shijie Li,&nbsp;Jiahao Hu,&nbsp;Jiasheng Cao,&nbsp;Cheeshin Lee,&nbsp;Yitong Tian,&nbsp;Mingyu Chen,&nbsp;Xiujun Cai","doi":"10.1002/aac2.12047","DOIUrl":"10.1002/aac2.12047","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>DNA molecules are subject to various lesions that can be detrimental to the cells. DNA damage response (DDR) pathways encompass a variety of mechanisms that cells employ in response to DNA damage. While DDR promotes genomic stability in normal cells, it also protects cancer cells from DNA lesions, particularly against exogenous DNA-damaging agents. Therefore, DDR pathways can be exploited to account for resistance to chemotherapy and radiotherapy and have the potential to be targeted in cancer treatment. Apart from the poly (ADP-ribose) polymerase (PARP) inhibitors used in BRCA-mutant cancers, other DDR inhibitors are being developed and tested in clinical trials. Based on the synthetic lethality theory, combination therapies utilizing DDR inhibitors have been explored and are currently undergoing clinical trials, with promising results in cancer treatment. Combination therapies typically employ a DDR inhibitor to sensitize cancer cells to traditional chemotherapeutic agents, radiotherapy, immunotherapy, and even PARP inhibitors. Herein, we focus on recent advances in DDR inhibitor-based combination therapies other than PARP inhibitors, explore the advantages and disadvantages of the strategies, and discuss the current challenges and future perspectives.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"3 1","pages":"44-67"},"PeriodicalIF":0.0,"publicationDate":"2022-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12047","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48480462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune checkpoint expression and relationships to anti-PD-L1 immune checkpoint blockade cancer immunotherapy efficacy in aged versus young mice","authors":"Myrna G. Garcia,&nbsp;Yilun Deng,&nbsp;Clare Murray,&nbsp;Ryan M Reyes,&nbsp;Alvaro Padron,&nbsp;Haiyan Bai,&nbsp;Aravind Kancharla,&nbsp;Harshita Gupta,&nbsp;Shai Shen-Orr,&nbsp;Tyler J. Curiel","doi":"10.1002/aac2.12045","DOIUrl":"10.1002/aac2.12045","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Aging is the biggest cancer risk, and immune checkpoint (IC) inhibition (ICI) is a revolutionary cancer immunotherapy approach. Nonetheless, there are limited preclinical/clinical data regarding aging effects on ICI outcomes or age effects on IC expression in different organs or tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Flow cytometry assessed IC on immune and non-immune cells in various organs in young and aged BL6 mice. Comparisons: aged versus young naïve WT versus interferon-γ^KO mice and WT challenged with B16F10 melanoma and treated with αPD-1 or αPD-L1 ICI. We co-cultured young and aged T cells and myeloid cells in vitro and used OMIQ analyses to test cell–cell interactions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>αPD-1 ICI treated melanoma in young and aged hosts, whereas αPD-L1 ICI was only effective in young. We found considerable, previously undescribed age effects on expression of various IC molecules participating in the ICI treatment, including PD-1, PD-L1, PD-L2, and CD80, in distinct organs and in the tumor. These data help explain differential ICI efficacy in young and aged hosts. Host interferon-γ influenced age effects on IC expression in both directions depending on specific IC molecule and tissue. IC expression was further affected by tumor challenge on immune, non-immune, and tumor cells in tumor and other organs. In in vitro co-culture, αPD-1 versus αPD-L1 distinctly influenced polyclonal T cells in young versus aged, suggesting mechanisms for distinct age-related ICI outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Age affects IC expression on specific immune cells in an organ- and tissue-specific manner. ICs were generally higher on aged immune cells. High immune-cell PD-1 could help explain αPD-1 efficacy in aged. High co-expression of CD80 with PD-L1 on dendritic cells could help explain lack of αPD-L1 efficacy in aged hosts. Factors other than myeloid cells and interferon-γ also affect age-related IC expression and T cell function, meriting additional studies.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"3 1","pages":"68-83"},"PeriodicalIF":0.0,"publicationDate":"2022-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980712/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10849985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The critical function of metabolic reprogramming in cancer metastasis","authors":"Sun-Zhe Xie,&nbsp;Jun-Jie Pan,&nbsp;Jian-Feng Xu,&nbsp;Wen-wei Zhu,&nbsp;Lun-Xiu Qin","doi":"10.1002/aac2.12044","DOIUrl":"10.1002/aac2.12044","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Cancer metastasis is the leading cause of cancer-related death. It is a complex, inefficient, and multistep process related to poor prognosis and high mortality of patients. Increasing evidence has shown that metabolic programming is a recognized hallmarker of cancer, plays a critical role in cancer metastasis. Metabolism alterations of glucose, lipid, and amino acid provide cancer cells with energy and substances for biosynthesis, maintain biofunctions and significantly affect proliferation, invasion, and metastasis of cancer cells. Tumor microenvironment (TME) is a complex system formed by varieties of cellular and noncellular elements. Nontumor cells in TME also undergo metabolic reprogramming or respond to metabolites to promote migration and invasion of cancer cells. A comprehensive understanding of the regulatory mechanism in metastasis from the metabolic reprogramming aspect is required to develop new therapeutic strategies combatting cancer metastasis. This review illustrates the metabolic reprogramming and interaction of cancer cells and nontumor cells in the TME, and the development of treatment strategies targeting metabolism alterations.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"3 1","pages":"20-43"},"PeriodicalIF":0.0,"publicationDate":"2022-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12044","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50805379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased risk of cancer in dogs and humans: A consequence of recent extension of lifespan beyond evolutionarily determined limitations?","authors":"Aaron L. Sarver,&nbsp;Kelly M. Makielski,&nbsp;Taylor A. DePauw,&nbsp;Ashley J. Schulte,&nbsp;Jaime F. Modiano","doi":"10.1002/aac2.12046","DOIUrl":"10.1002/aac2.12046","url":null,"abstract":"<p>Cancer is among the most common causes of death for dogs (and cats) and humans in the developed world, even though it is uncommon in wildlife and other domestic animals. We provide a rationale for this observation based on recent advances in our understanding of the evolutionary basis of cancer. Over the course of evolutionary time, species have acquired and fine-tuned adaptive cancer-protective mechanisms that are intrinsically related to their energy demands, reproductive strategies, and expected lifespan. These cancer-protective mechanisms are general across species and/or specific to each species and their niche, and they do not seem to be limited in diversity. The evolutionarily acquired cancer-free longevity that defines a species’ life history can explain why the relative cancer risk, rate, and incidence are largely similar across most species in the animal kingdom despite differences in body size and life expectancy. The molecular, cellular, and metabolic events that promote malignant transformation and cancerous growth can overcome these adaptive, species-specific protective mechanisms in a small proportion of individuals, while independently, some individuals in the population might achieve exceptional longevity. In dogs and humans, recent dramatic alterations in healthcare and social structures have allowed increasing numbers of individuals in both species to far exceed their species-adapted longevities (by two to four times) without allowing the time necessary for compensatory natural selection. In other words, the cancer-protective mechanisms that restrain risk at comparable levels to other species for their adapted lifespan are incapable of providing cancer protection over this recent, drastic, and widespread increase in longevity.</p>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"3 1","pages":"3-19"},"PeriodicalIF":0.0,"publicationDate":"2022-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387675/pdf/nihms-1778919.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10810844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physical activity and fitness in childhood cancer survivors: A scoping review","authors":"Matthew D. Wogksch,&nbsp;Chelsea G. Goodenough,&nbsp;Emily R. Finch,&nbsp;Robyn E. Partin,&nbsp;Kirsten K. Ness","doi":"10.1002/aac2.12042","DOIUrl":"10.1002/aac2.12042","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Estimates indicate that nearly 8% of the over 500,000 survivors of childhood cancer living in the United States are frail in their fourth and fifth decades of life, a phenotype typically seen in geriatric populations. Participation in regular physical activity to improve physical fitness in healthy and diseased populations reduces risk for frail health by increasing physiologic reserve. However, physical activity may not have the same effects on fitness in childhood cancer survivors as it does among their peers with no cancer history.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>This scoping review seeks to describe associations between physical activity, physical fitness, chronic disease, and mortality in childhood cancer survivors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Relevant literature was identified through a comprehensive search in the PubMed, Web of Science, CINAHL, and Cochrane databases. A narrative synthesis was performed on observational studies that had physical activity or physical fitness clearly defined and compared with chronic disease outcomes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 595 studies were screened, and results from 11 studies are presented. Childhood cancer survivors who participate in regular physical activity have improved markers of cardiovascular health, decreased risk of overt cardiovascular disease, and decreased risk of all-cause mortality compared to survivors who are not physically active. Childhood cancer survivors who are physically fit have increased neurocognition, and decreased risk of all-cause mortality compared to survivor's who are not fit. The differential effects of physical activity on fitness and health among childhood cancer survivors when compared to peers is potentially related to treatment exposures that damage cardiovascular tissue and impact regenerative potential.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Research is needed to determine the optimal timing, frequency, intensity, and duration of physical activity necessary to optimize fitness in childhood cancer survivors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"112-128"},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8794406/pdf/nihms-1772678.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10399994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXO3 regulates a common genomic program in aging and glioblastoma stem cells","authors":"Amanda J. Audesse,&nbsp;Galina Karashchuk,&nbsp;Zachary A. Gardell,&nbsp;Nelli S. Lakis,&nbsp;Sun Y. Maybury-Lewis,&nbsp;Abigail K. Brown,&nbsp;Dena S. Leeman,&nbsp;Yee Voan Teo,&nbsp;Nicola Neretti,&nbsp;Douglas C. Anthony,&nbsp;Alexander S. Brodsky,&nbsp;Ashley E. Webb","doi":"10.1002/aac2.12043","DOIUrl":"10.1002/aac2.12043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Glioblastoma (GBM) is an aggressive, age-associated malignant glioma that contains populations of cancer stem cells. These glioma stem cells (GSCs) evade therapeutic interventions and repopulate tumors due to their existence in a slowly cycling quiescent state. Although aging is well known to increase cancer initiation, the extent to which the mechanisms supporting GSC tumorigenicity are related to physiological aging remains unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>Here, we investigate the transcriptional mechanisms by which Forkhead Box O3 (FOXO3), a transcriptional regulator that promotes healthy aging, affects GSC function and the extent to which FOXO3 transcriptional networks are dysregulated in aging and GBM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and results</h3>\u0000 \u0000 <p>We performed transcriptome analysis of clinical GBM tumors and observed that high FOXO3 activity is associated with gene expression signatures of stem cell quiescence, reduced oxidative metabolism, and improved patient outcomes. Consistent with these findings, we show that elevated FOXO3 activity significantly reduces the proliferation of GBM-derived GSCs. Using RNA-seq, we find that functional ablation of FOXO3 in GSCs rewires the transcriptional circuitry associated with metabolism, epigenetic stability, quiescence, and differentiation. Since FOXO3 has been implicated in healthy aging, we then investigated the extent to which it regulates common transcriptional programs in aging neural stem cells (NSCs) and GSCs. We uncover a shared transcriptional program and, most strikingly, find that FOXO3-regulated pathways are associated with altered mitochondrial functions in both aging and GBM.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This work identifies a FOXO-associated transcriptional program that correlates between GSCs and aging NSCs and is enriched for metabolic and stemness pathways connected with GBM and aging.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"137-159"},"PeriodicalIF":0.0,"publicationDate":"2021-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9601604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10513726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term analysis of irradiated skin after breast-conserving surgery in breast cancer patients using noninvasive imaging","authors":"Kasumi Mikami,&nbsp;Maiko Kitajima,&nbsp;Yuka Noto,&nbsp;Chieko Itaki,&nbsp;Yasuyo Fukushi,&nbsp;Yoshiko Hirota,&nbsp;Yasushi Mariya,&nbsp;Megumi Tsushima,&nbsp;Keiichi Kattou,&nbsp;Tomohiro Osanai","doi":"10.1002/aac2.12041","DOIUrl":"10.1002/aac2.12041","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In patients with breast cancer, skin assessment is useful for the treatment and prevention of postoperative adverse effects of radiotherapy. This study was designed to clarify the long-term changes in the irradiated skin of patients after breast-conserving surgery using visual inspection and noninvasive imaging.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We compared changes in the irradiated skin over time between evaluations, based on visual inspection and noninvasive imaging in 31 patients receiving postmastectomy radiation therapy. The condition of the skin was evaluated by visual inspection of the thermogram, and analysis of skin surface temperature, intensity of erythema, intensity of melanin, and hydration level.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Skin surface temperature remained higher at the irradiation site after 11 months, despite the absence of erythema per visual inspection. The intensity of erythema was higher at the irradiated site until 17–19 months after completion of irradiation. Similarly, the intensity of melanin tended to be higher at the irradiated site compared with the nonirradiated site until 17–19 months. The hydration level at the irradiated site was lower at 6 months but recovered to match the nonirradiated site at 11–13 months. Impaired skin conditions assessed by noninvasive objective procedures persist longer than the assessment made by visual inspection.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Adverse effects should be treated or prevented in the long term in patients receiving postmastectomy radiation therapy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"129-136"},"PeriodicalIF":0.0,"publicationDate":"2021-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48284533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An outlook on the lymph nodes dissection during the pancreatectomy for pancreatic cancer","authors":"Weishen Wang,&nbsp;Baiyong Shen","doi":"10.1002/aac2.12040","DOIUrl":"10.1002/aac2.12040","url":null,"abstract":"<p>Pancreatic cancer is likely to be one of the most highly lethal diseases in the world.<span>^{1, 2}</span> Radical pancreatectomy with adjuvant chemotherapy is a curative treatment for pancreatic cancer.<span>²</span> Lymphadenectomy is an indispensable procedure in radical resection for pancreatic cancer. It is obvious that lymph node dissection is essential. According to the eight edition of the American Joint Committee on Cancer (AJCC) tumor node metastasis (TNM) staging system, the number of positive lymph nodes (PLNs) is related to the prognosis of the patients.<span>³</span> Moreover, a standard lymphadenectomy reduces the incidence of local lymph node recurrence.<span>^{4, 5}</span> However, in some cases, the current guidelines or consensus cannot be satisfied in clinical practice. Thus, in this brief literature review, we summarize the current status of lymph nodes dissection in pancreatectomy while focusing on the further development of research.</p><p>The AJCC TNM staging system is the most worldwide used system that provides us a relatively accurate prognosis of the patients. The latest version is the eight edition of the TNM staging system.<span>³</span> The main revision to the seventh edition is the modification of the N status in the system. Previously, in the seventh edition, the N status was separated into N0/N1 depending on whether regional metastatic lymph nodes were found in the operation. The impact of the number of PLNs on the prognosis was ignored. Currently, in the eight edition, the N status is divided into N0/N1/N2 based on the number of PLNs. The patients without lymph node metastasis are stated in the N0 stage. The patients with four or more PLNs are classified into the N2 stage, which implied poor survival. The rest are in the N1 stage whose PLNs are less than four.</p><p>In order to acquire accurate PLNs, a certain number of lymph nodes should be harvested. The optimal lymphadenectomy was disputed until a consensus statement on the extent of lymphadenectomy for pancreatectomy was published by the International Study Group on Pancreatic Surgery (ISGPS) in 2014.<span>⁴</span> In this statement, the study group has affirmed the extent of lymph node dissection for the pancreatectomy. Based on the nomenclature for nodal stations of the Japanese Pancreas Society,<span>⁶</span> a standard lymphadenectomy should include lymph node stations 5, 6, 8a, 12b1, 12b2, 12c, 13a, 13b, 14a right lateral side, 14b right lateral side, 17a, and 17b during the pancreatoduodenectomy (PD), while a standard lymphadenectomy during the distal pancreatectomy should include lymph node stations 10, 11 and 18 for the tumor located in the body and tail of the pancreas. Furthermore, the minimal number of examined lymph nodes (MNELN) for the PD was considered to be at least 15. With the increase of the number of regional lymph nodes retrieved, the accuracy of PLNs raised up.<s","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 4","pages":"107-111"},"PeriodicalIF":0.0,"publicationDate":"2021-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49206462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Flatten the rising incidence of cancer due to aging","authors":"Samuel Waxman","doi":"10.1002/aac2.12039","DOIUrl":"10.1002/aac2.12039","url":null,"abstract":"<p>As an oncologist engaged for 45 years in providing ongoing patient care I witnessed a cancer treatment revolution. Multiple options to conventional cytotoxic chemotherapy emerged that led to changing cancer from a rapid fatal disease to a more treatable chronic ailment.  Science was paying off by diminishing the catastrophic effect of cancer for a large number of patients. More people were being cured with less toxic treatments. A significant gain in outcome BUT, my patients were returning with late onset metastases and new primary cancers, this time more difficult to treat and often  associated with the  comorbidities of AGING. This scenario is a global experience. Cancer incidence is increasing in most forms of cancer and mortality rates rising relentlessly with increasing age. The reality is that understanding AGE-related cancer, its evolution, interplay, clinical recognition, and management is underfunded and is an unmet clinical need. As recently as 2015, there has been minimal interactions between the National Cancer Institute and the National Aging Institute to promote research at the interface of aging and cancer, despite the overt links between these processes. Indeed, a major DISPARITY both in research and treating age-related cancer exists.</p><p>Yet, ANSWERS are within reach to guide collaborative research to flatten the rising incidence of cancer due to aging. A more holistic view for how aging impacts cancer gaining ground. Aging stem and progenitor cells strive to survive in a changing and often hostile aging stromal environment. This results in somatic variants, epigenetic compensations, loss of gene stability due to DNA damage, and mechanisms to resist exhaustion and death such as reducing immune recognition and hijacking senescence and autophagy  pathways for survival. These changes may be apparent by measurement of clonal progenitor populations with mutations allowing epigenetic driven pathways and cell cycle alterations to emerge to create a survival advantage. Is this privileged and more compensated AGED cell an outlier that is already on a path to cancer clonal evolution and can this be prevented? Clinical and laboratory evidence supports this and  collaborative research is providing models to understand ways to recognize this  transition and identify this threat with precision in the aging cell population. Interventions to diminish age as a risk factor for cancer include education on the importance of “Healthy Aging” and laboratory measurements to distinguish a healthy aged tissue from one with cancerous clonal evolution. Therapeutic interventions to diminish  cancer development in the AGED cell population include early clinical screening, senolytics, specific inhibitors of cell cycle mediators of autophagy, PARP inhibitors, and identifying specific dietary and metabolic dependencies needed to prevent cancer transformation. This type of early screening of AGING stem cells and progenitors and evolving clonal cancer cells ","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 3","pages":"73"},"PeriodicalIF":0.0,"publicationDate":"2021-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50805305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to the third issue of Aging and Cancer","authors":"Doris Germain PhD","doi":"10.1002/aac2.12038","DOIUrl":"10.1002/aac2.12038","url":null,"abstract":"<p>Dr. Samuel Waxman has dedicated his career to the treatment of cancer patients and to cancer research. While he led an extraordinarily successful medical practice for 45 years, he understood very early that knowledge is power and that without research, cancer treatment would remain highly toxic.</p><p>His passion for research is best illustrated by the creation of the Samuel Waxman Cancer Research Foundation (SWCRF) in 1976. The SWCRF currently funds a network of 30 researchers across the world and raised over $100 million for cancer research.</p><p>To this day, the passion of this remarkable physician-scientist has only become stronger. His most recent goal is to understand the link between cancer and aging. While cancer is known to be an age-related disease, surprisingly, little research focuses on how and why cancer is more frequent in older individuals.</p><p>Dr. Waxman has, therefore, not only established collaboration between his foundation and the National Institute of Aging to specifically fund research projects aimed at understanding the link between aging and cancer but also teamed up with Wiley Publishing to launch this new journal in 2020.</p><p>In this third edition of <i>Aging and Cancer</i>, three articles from SWCRF investigators were selected to illustrate the range of questions and approaches needed to cover the complexity of the link between aging and cancer.</p><p>The first article by our group (Jenkins et al. Are the estrogen receptor and SIRT3 axes of the mitochondrial UPR key regulators of breast cancer sub-type determination according to age? Aging and Cancer, 2021. https://doi.org/10.1002/aac2.12035) focuses on the counterintuitive observation that breast cancer in post-menopausal women, which have much lower levels of circulating estrogen due to the cessation of ovarian function at menopause, tends to develop cancers that show elevated expression of the estrogen receptor.</p><p>The second article by Edward Evans and SWCRF investigator James DeGregori (Evans et al. Cells with Cancer-associated Mutations Overtake Our Tissues as We Age. Aging and Cancer, 2021) uses an unbiased approach of a meta-analysis of published sequencing data on normal tissues to determine how many cancer-associated mutations are present in cancer-free individuals with age. They present evidence that these mutations are actually found at high frequency across tissues. This finding immediately raises the question as to why some individuals go on to develop cancer, while others do not.</p><p>In direct line with the Evans study, the third article by SWCRF-associated investigator Paolo Boffetta and colleagues (Franchi et al. Developing a multimorbidity prognostic score in elderly patients with solid cancer using administrative databases from Italy. <i>Aging and Cancer</i>, 2021) takes an epidemiological approach to interrogate multiple conditions and their association with Cancer Multimorbidity Score (CMS). Their study suggests that the CMS may be use","PeriodicalId":72128,"journal":{"name":"Aging and cancer","volume":"2 3","pages":"74"},"PeriodicalIF":0.0,"publicationDate":"2021-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/aac2.12038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43003913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}