Системные факторы противодействия вкладу обратимых переходов злокачественных клеток между фенотипическими состояниями в резистентность к терапии
pdf

Ключевые слова

резистентность к противоопухолевой терапии
фенотипическая пластичность
метаболизм
старение
антидиабетические бигуаниды

Аннотация

Анализ литературы, имеющей отношение к фенотипической пластичности трансформированных клеток при развитии резистентности опухолей к терапии, привел с учетом основных характеристик эпителиального, мезенхимального, стволового и сенесцентного состояний опухолевых клеток к выводу, что ключевым фактором терапевтической резистентности является обратимость переходов между этими состояниями. Молекулярные механизмы таких переходов могут включать стохастические переключения активных генов между участием и неучастием в транскрипции. Кинетика переходов и соответствующее равновесие между разными фенотипическими состояниями существенно зависят от среды, где это происходит, а значит от возраста опухоленосителя и от его гормонально-метаболического статуса. Таким образом, воздействия на метаболические параметры организма могут влиять на эффективность противоопухолевой терапии без изменений жизнеспособности и пролиферации опухолевых клеток в любом из возможных для них состояний. С таких позиций рассмотрены данные о противоопухолевых эффектах антидиабетических бигуанидов. Сделан вывод, что, если анализировать в терминах обратимости фенотипических состояний трансформированных клеток противоопухолевые эффекты воздействий, цитотоксические или цитостатические последствия которых неочевидны, это может не только помочь в понимании того, каким образом такие воздействия могут влиять на опухоли, но и расширить круг критериев для поисков новых противораковых средств.
https://doi.org/10.37469/0507-3758-2022-68-6-708-716
pdf

Библиографические ссылки

Nowell PC. The clonal evolution of tumor cell populations // Science. 1976;194:23–8.

Nussinov R, Tsai C-J, Jang H. Anticancer drug resistance: An update and perspective // Drug Resist Updates. 2021;59:100796. doi:10.1016/j.drup.2021.100796

Aleksakhina SN, Kashyap A, Imyanitov EN. Mechanisms of acquired tumor drug resistance // Biochim Biophys Acta Rev Cancer. 2019;1872:188310. doi:10.1016/j.bbcan.2019.188310

Welch DR, Hurst DR. Defining the hallmarks of metastasis // Cancer Res. 2019;79:3011–27.

Settleman J, Neto JMF, Bernards R. Thinking differently about cancer treatment regimens // Cancer Discov. 2021;11:1016–23.

Viossat Y, Noble R. A theoretical analysis of tumour containment // Nat Ecol Evolut. 2021;5:826–35.

Karabicici M, Alptekin S, Fırtına Karagonlar Z, Erdal E. Doxorubicin-induced senescence promotes stemness and tumorigenicity in EpCAM-/CD133- nonstem cell population in hepatocellular carcinoma cell line, HuH-7 // Mol Oncol. 2021;15:2185–202.

Welte Y, Adjaye J, Lehrach HR, Regenbrecht CRA. Cancer stem cells in solid tumors: elusive or illusive? // Cell Communicat Signal. 2010;8:6. doi:10.1186/1478-811X-8-6

Quintana E, Shackleton M, Foster HR et al. Phenotypic heterogeneity among tumorigenic melanoma cells from patients that is reversible and not hierarchically organized // Cancer Cell. 2010;18:510–23.

Rumman M, Dhawan J, Kassem M. Concise review: Quiescence in adult stem cells: Biological significance and relevance to tissue regeneration // Stem Cells. 2015;33:2903–12.

Thiery JP, Acloque H, Huang RYJ, Nieto MA. Epithelial-mesenchymal transitions in development and disease // Cell. 2009;139:871–90.

Sheng G. Defining epithelial-mesenchymal transitions in animal development // Development. 2021;148(8). doi:10.1242/dev.198036

Pastushenko I, Brisebarre A, Sifrim A et al. Identification of the tumour transition states occurring during EMT // Nature. 2018;556:463–8.

Emert BL, Cote CJ, Torre EA et al. Variability within rare cell states enables multiple paths toward drug resistance // Nat Biotechnol. 2021;39:865–76.

Sahoo S, Ashraf B, Duddu AS et al. Interconnected high-dimensional landscapes of epithelial–mesenchymal plasticity and stemness in cancer // Clin Exper Metastasis. 2022. doi:10.1007/s10585-021-10139-2

Willet SG, Lewis MA, Miao Z-F et al. Regenerative proliferation of differentiated cells by mTORC1-dependent paligenosis // EMBO J. 2018;37:e98311. doi:10.15252/embj.201798311

Mills JC, Stanger BZ, Sander M. Nomenclature for cellular plasticity: are the terms as plastic as the cells themselves? // EMBO J. 2019;38:e103148. doi:10.15252/embj.2019103148

Nami B, Ghanaeian A, Black C, Wang Z. Epigenetic silencing of HER2 expression during epithelial-mesenchymal transition leads to trastuzumab resistance in breast cancer // Life. 2021;11:868. doi:10.3390/life11090868

Nami B, Ghanaeian A, Black C, Wang Z. Epigenetic silencing of HER2 expression during epithelial-mesenchymal transition leads to trastuzumab resistance in breast cancer // Life. 2021;11:868. doi:10.3390/life11090868

Shay JW, Wright WE. Senescence and immortalization: role of telomeres and telomerase // Carcinogenesis. 2004;26:867–74.

Krishnamurthy J, Torrice C, Ramsey MR et al. Ink4a/Arf expression is a biomarker of aging // J Clin Invest. 2004;114:1299–307.

Wolf AM. The tumor suppression theory of aging // Mech Ageing Develop. 2021;200:111583. doi:10.1016/j.mad.2021.111583

Hernandez-Segura A, Nehme J, Demaria M. Hallmarks of Cellular Senescence // Trends Cell Biol. 2018;28:436–53.

Sharpless NE, Sherr CJ. Forging a signature of in vivo senescence // Nat Rev Cancer. 2015;15:397–408.

Prokhorova EA, Egorshina AY, Zhivotovsky B, Kopeina GS. The DNA-damage response and nuclear events as regulators of nonapoptotic forms of cell death // Oncogene. 2020;39:1–16.

Inomata K, Aoto T, Binh NT et al. Genotoxic stress abrogates renewal of melanocyte stem cells by triggering their differentiation // Cell. 2009;137:1088–99.

Schneider L, Pellegatta S, Favaro R et al. DNA damage in mammalian neural stem cells leads to astrocytic differentiation mediated by BMP2 signaling through JAK-STAT // Stem Cell Rep. 2013;1:123–38.

Golomb L, Sagiv A, Pateras IS et al. Age-associated inflammation connects RAS-induced senescence to stem cell dysfunction and epidermal malignancy // Cell Death Differ. 2015;22:1764–74.

Wang L, Lankhorst L, Bernards R. Exploiting senescence for the treatment of cancer // Nat Rev Cancer. 2022. doi:10.1038/s41568-022-00450-9

Demaria M, Ohtani N, Youssef Sameh A et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA // Develop Cell. 2014;31:722–33.

Storer M, Mas A, Robert-Moreno A et al. Senescence is a developmental mechanism that contributes to embryonic growth and patterning // Cell. 2013;155:1119–30.

Li Y, Zhao H, Huang X et al. Embryonic senescent cells re-enter cell cycle and contribute to tissues after birth // Cell Res. 2018;28:775–8.

Tripathi U, Misra A, Tchkonia T, Kirkland JL. Impact of senescent cell subtypes on tissue dysfunction and repair: Importance and research questions // Mech Ageing Develop. 2021;198:111548. doi:10.1016/j.mad.2021.111548

Sikora E, Bielak-Zmijewska A, Mosieniak G. A common signature of cellular senescence; does it exist? // Ageing Res Rev. 2021;71:101458. doi:10.1016/j.arr.2021.101458

Golubev AG, Khrustalev S, Butov AA. An in silico investigation into the causes of telomere length heterogeneity and its implications for the Hayflick limit // J Theor Biol. 2003;225:153–70.

Adler FR, Amend SR, Whelan CJ, Baratchart E. From Ecology to Cancer Biology and Back Again // Frontiers Media SA. 2022.

Голубев АГ. Общие принципы взаимоотношений живых организмов с экосистемой и злокачественных клеток с живым организмом // Биосфера. 2022;14:61–74 [Golubev AG. Common principles of interelationships between living organbisms and an ecosystem and between malignant cells and a living organism // Biosfera. 2022;14:61–74 (In Russ.)].

Denmeade S, Antonarakis ES, Markowski MC. Bipolar androgen therapy (BAT): A patient's guide // Prostate. 2022;82:753–62.

Zhang J, Cunningham J, Brown J, Gatenby R. Evolution-based mathematical models significantly prolong response to abiraterone in metastatic castrate-resistant prostate cancer and identify strategies to further improve outcomes // Life. 2022;11:e76284.

Gunnarsson EB, De S, Leder K, Foo J. Understanding the role of phenotypic switching in cancer drug resistance // J Theor Biol. 2020;490:110162. doi:10.1016/j.jtbi.2020.110162

Fane M, Weeraratna AT. How the ageing microenvironment influences tumour progression // Nat Rev Cancer. 2020;20:89–106.

Bouleftour W, Magne N. Aging preclinical models in oncology field: from cells to aging // Aging Clin Exper Res. 2021. doi 10.1007/s40520-021-01981-1:

Habr D, McRoy L, Papadimitrakopoulou VA. Age is just a number: Considerations for older adults in cancer clinical trials // J Natl Cancer Inst. 2021;113:1460–4.

Golubev AG, Anisimov VN. Aging and cancer: Is glucose a mediator between them? // Oncotarget. 2019;10:6758–67.

Li S, Zhu H, Chen H et al. Glucose promotes epithelial-mesenchymal transitions in bladder cancer by regulating the functions of YAP1 and TAZ // J Cell Mol Med. 2020;24:10391–401.

Li W, Zhang L, Chen X et al. Hyperglycemia promotes the epithelial-mesenchymal transition of pancreatic cancer via hydrogen peroxide // Oxid Med Cell Longev. 2016. doi:10.1155/2016/5190314

Wu J, Chen J, Xi Y et al. High glucose induces epithelial‑mesenchymal transition and results in the migration and invasion of colorectal cancer cells // Exper Therap Med. 2018;16:222–30.

Anisimov VN. Metformin for cancer and aging prevention: is it a time to make the long story short? // Oncotarget. 2015;6:39398–407.

Dilman VM, Anisimov VN. Potentiation of antitumor effect of cyclophosphamide and hydrazine sulfate by treatment with the antidiabetic agent, 1-phenylethylbiguanide (phenformin) // Cancer Lett. 1979;7:357–61.

Alexandrov VA, Anisimov VN, Belous NM et al. The inhibition of the transplacental blastomogenic effect of nitrosomethylurea by postnatal administration of buformin to rats // Carcinogenesis. 1980;1:975–8.

Dilman VM, Revskoy SY, Golubev AG. Neuroendocrine-ontogenetic mechanism of aging: toward an integrated theory of aging // Int Rev Neurobiol. 1986;28:89–156.

Samuel SM, Varghese E, Koklesová L et al. Counteracting chemoresistance with metformin in breast cancers: Targeting cancer stem cells // Cancers. 2020;12. doi:10.3390/cancers12092482

Di Matteo S, Nevi L, Overi D et al. Metformin exerts anti-cancerogenic effects and reverses epithelial-to-mesenchymal transition trait in primary human intrahepatic cholangiocarcinoma cells // Sci Rep. 2021;11:2557. doi:10.1038/s41598-021-81172-0

Patil S. Metformin treatment decreases the expression of cancer stem cell marker CD44 and stemness related gene expression in primary oral cancer cells // Arch Oral Biol. 2020;113:104710. doi:10.1016/j.archoralbio.2020.104710

Yin W, Liu Y, Liu X et al. Metformin inhibits epithelial-mesenchymal transition of oral squamous cell carcinoma via the mTOR/HIF-1α/PKM2/STAT3 pathway // Oncol Lett. 2021;21:31. doi:10.3892/ol.2020.12292

Seo Y, Kim J, Park SJ et al. Metformin suppresses cancer stem cells through AMPK activation and inhibition of protein prenylation of the mevalonate pathway in colorectal cancer // Cancers. 2020;12. doi 10.3390/cancers12092554:

Zhang C, Wang Y. Metformin attenuates cells stemness and epithelial‑mesenchymal transition in colorectal cancer cells by inhibiting the Wnt3a/β‑catenin pathway // Mol Med Rep. 2019;19:1203–9.

Deschênes-Simard X, Parisotto M, Rowell M-C et al. Circumventing senescence is associated with stem cell properties and metformin sensitivity // Aging Cell. 2019;18:e12889. doi:10.1111/acel.12889

Zahra MH, Afify SM, Hassan G et al. Metformin suppresses self-renewal and stemness of cancer stem cell models derived from pluripotent stem cells // Cell Biochem Funct 2021;39:896–907.

Park JH, Kim YH, Park EH et al. Effects of metformin and phenformin on apoptosis and epithelial-mesenchymal transition in chemoresistant rectal cancer // Cancer Sci. 2019;110:2834–45.

Zhao H, Swanson KD, Zheng B. Therapeutic repurposing of biguanides in cancer // Trends Cancer. 2021;7:714–30.

Kuo CL, Hsieh Li SM, Liang SY et al. The antitumor properties of metformin and phenformin reflect their ability to inhibit the actions of differentiated embryo chondrocyte 1 // Cancer Manag Res. 2019;11:6567–79.

García Rubiño ME, Carrillo E, Ruiz Alcalá G et al. Phenformin as an anticancer agent: Challenges and prospects // Int J Mol Sci. 2019;20. doi:10.3390/ijms20133316

Vara-Ciruelos D, Dandapani M, Russell FM et al. Phenformin, but not metformin, delays development of T cell acute lymphoblastic leukemia/lymphoma via cell-autonomous AMPK activation // Cell Rep. 2019;27:690–8.e4. doi:10.1016/j.celrep.2019.03.067

Дильман ВМ, Берштейн ЛМ, Цырлина ЕВ и др. Коррекция эндокринно-метаболических нарушений у онкологических больных. Эффекты бигуанидов (фенформин и адебита), мисклерона и дифенина // Вопросы онкологии. 1975;21(11):33–9 [Dilman VM, Bershtein LM, Tsyrlina YeV et al. Correction of endorine-metabolic disorders in cancer patients. The effects of biguanides (phenformin and adebit), miscleron and diphenin // Voprosy onkologii. 1975;21(11):33–9 (In Russ.)].

Vidoni C, Ferraresi A, Esposito A et al. Calorie restriction for cancer prevention and therapy: Mechanisms, expectations, and efficacy // J Cancer Prevent. 2021;26:224–36.

Golubev AG. Commentary: Is life extension today a Faustian bargain? // Front Med. 2018;5. doi:10.3389/fmed.2018.00073

Golubev AG. COVID-19: A challenge to physiology of aging // Front Physiol. 2020;11. doi:10.3389/fphys.2020.584248

Голубев АГ, Семиглазова ТЮ, Клюге ВА и др. Три пандемии сразу: неинфекционная (онкологическая), инфекционная (CoVID-19) и поведенческая (гипокинезия) // Вопросы онкологии. 2021;67(2):163–80 [Golubev AG, Semiglazova TY, Klyuge VA et al. Three pandemics at once: noninfectious (cancer), infectious (COVID-19), and behavioral (hypokinesia) // Voprosy onkologii. 2021;67(2):163–80 (In Russ.)].

Yang H, Liu Y, Kong J. Effect of aerobic exercise on acquired gefitinib resistance in lung adenocarcinoma // Translat Oncol. 2021;14:101204. doi:10.1016/j.tranon.2021.101204

Лицензия Creative Commons

Это произведение доступно по лицензии Creative Commons «Attribution-NonCommercial-NoDerivatives» («Атрибуция — Некоммерческое использование — Без производных произведений») 4.0 Всемирная.

Copyright (c) 2022 Алексей Георгиевич Голубев, Владимир Николаевич Анисимов