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  1. Article: My battle with cancer. Part 1.

    Blagosklonny, Mikhail V

    Oncoscience

    2024  Volume 11, Page(s) 1–14

    Abstract: In January 2023, diagnosed with numerous metastases of lung cancer in my brain, I felt that I must accomplish a mission. If everything happens for a reason, my cancer, in particular, I must find out how metastatic cancer can be treated with curative ... ...

    Abstract In January 2023, diagnosed with numerous metastases of lung cancer in my brain, I felt that I must accomplish a mission. If everything happens for a reason, my cancer, in particular, I must find out how metastatic cancer can be treated with curative intent. This is my mission now, and the reason I was ever born. In January 2023, I understood the meaning of life, of my life. I was born to write this article. In this article, I argue that monotherapy with targeted drugs, even when used in sequence, cannot cure metastatic cancer. However, preemptive combinations of targeted drugs may, in theory, cure incurable cancer. Also, I share insights on various topics, including rapamycin, an anti-aging drug that can delay but not prevent cancer, through my personal journey.
    Language English
    Publishing date 2024-01-03
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2331-4737
    ISSN 2331-4737
    DOI 10.18632/oncoscience.593
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: From osimertinib to preemptive combinations.

    Blagosklonny, Mikhail V

    Oncotarget

    2024  Volume 15, Page(s) 232–237

    Abstract: Here, I suggest that while first-line osimertinib extends median progression-free survival (PFS) in EGFR-mutant lung cancer compared to first-generation TKIs, it reduces individual PFS in 15-20% of patients compared to first-generation TKIs. Since ... ...

    Abstract Here, I suggest that while first-line osimertinib extends median progression-free survival (PFS) in EGFR-mutant lung cancer compared to first-generation TKIs, it reduces individual PFS in 15-20% of patients compared to first-generation TKIs. Since detecting a single resistant cell before treatment is usually impossible, osimertinib must be used in all patients as a first-line treatment, raising median PFS overall but harming some. The simplest remedy is a preemptive combination (PC) of osimertinib and gefitinib. A comprehensive PC (osimertinib, afatinib/gefitinib, and capmatinib) could dramatically increase PFS for 80% of patients compared to osimertinib alone, without harming anyone. This article also explores PCs for MET-driven lung cancer.
    MeSH term(s) Humans ; Gefitinib ; Acrylamides ; Afatinib ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Aniline Compounds ; Indoles ; Pyrimidines
    Chemical Substances osimertinib (3C06JJ0Z2O) ; Gefitinib (S65743JHBS) ; Acrylamides ; Afatinib (41UD74L59M) ; Aniline Compounds ; Indoles ; Pyrimidines
    Language English
    Publishing date 2024-03-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.28569
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Cellular senescence: when growth stimulation meets cell cycle arrest.

    Blagosklonny, Mikhail V

    Aging

    2023  Volume 15, Issue 4, Page(s) 905–913

    Abstract: At the very moment of cell-cycle arrest, the cell is not senescent yet. For several days in cell culture, the arrested cell is acquiring a senescent phenotype. What is happening during this geroconversion? Cellular enlargement (hypertrophy) and ... ...

    Abstract At the very moment of cell-cycle arrest, the cell is not senescent yet. For several days in cell culture, the arrested cell is acquiring a senescent phenotype. What is happening during this geroconversion? Cellular enlargement (hypertrophy) and hyperfunctions (lysosomal and hyper-secretory) are hallmarks of geroconversion.
    MeSH term(s) Cell Cycle Checkpoints/genetics ; Cellular Senescence/genetics ; Cell Proliferation
    Language English
    Publishing date 2023-02-19
    Publishing country United States
    Document type Journal Article
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.204543
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Are menopause, aging and prostate cancer diseases?

    Blagosklonny, Mikhail V

    Aging

    2023  Volume 15, Issue 2, Page(s) 298–307

    Abstract: There is no doubt that prostate cancer is a disease. Then, according to hyperfunction theory, menopause is also a disease. Like all age-related diseases, it is a natural process, but is also purely harmful, aimless and unintended by nature. But exactly ... ...

    Abstract There is no doubt that prostate cancer is a disease. Then, according to hyperfunction theory, menopause is also a disease. Like all age-related diseases, it is a natural process, but is also purely harmful, aimless and unintended by nature. But exactly because these diseases (menopause, prostate enlargement, obesity, atherosclerosis, hypertension, diabetes, presbyopia and thousands of others) are partially quasi-programmed, they can be delayed by slowing aging. Is aging a disease? Aging is a quasi-programmed disease that is partially treatable by rapamycin. On the other hand, aging is an abstraction, a sum of all quasi-programmed diseases and processes. In analogy, the zoo consists of animals and does not exist without animals, but the zoo is not an animal.
    MeSH term(s) Humans ; Male ; Animals ; Aging ; Menopause ; Sirolimus ; Prostatic Neoplasms ; Longevity
    Chemical Substances Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2023-01-26
    Publishing country United States
    Document type Journal Article
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.204499
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Towards disease-oriented dosing of rapamycin for longevity: does aging exist or only age-related diseases?

    Blagosklonny, Mikhail V

    Aging

    2023  Volume 15, Issue 14, Page(s) 6632–6640

    Abstract: Both individuals taking rapamycin, an anti-aging drug, and those not taking it will ultimately succumb to age-related diseases. However, the former, if administered disease-oriented dosages for a long time, may experience a delayed onset of such diseases ...

    Abstract Both individuals taking rapamycin, an anti-aging drug, and those not taking it will ultimately succumb to age-related diseases. However, the former, if administered disease-oriented dosages for a long time, may experience a delayed onset of such diseases and live longer. The goal is to delay a particular disease that is expected to be life-limiting in a particular person. Age-related diseases, quasi-programmed during development, progress at varying rates in different individuals. Rapamycin is a prophylactic anti-aging drug that decelerates early development of age-related diseases. I further discuss hyperfunction theory of quasi-programmed diseases, which challenges the need for the traditional concept of aging itself.
    MeSH term(s) Humans ; Longevity ; Sirolimus/pharmacology ; Aging
    Chemical Substances Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Journal Article
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.204920
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells.

    Blagosklonny, Mikhail V

    Oncotarget

    2023  Volume 14, Page(s) 193–206

    Abstract: Cancer therapy is limited by toxicity in normal cells and drug-resistance in cancer cells. Paradoxically, cancer resistance to certain therapies can be exploited for protection of normal cells, simultaneously enabling the selective killing of resistant ... ...

    Abstract Cancer therapy is limited by toxicity in normal cells and drug-resistance in cancer cells. Paradoxically, cancer resistance to certain therapies can be exploited for protection of normal cells, simultaneously enabling the selective killing of resistant cancer cells by using antagonistic drug combinations, which include cytotoxic and protective drugs. Depending on the mechanisms of drug-resistance in cancer cells, the protection of normal cells can be achieved with inhibitors of CDK4/6, caspases, Mdm2, mTOR, and mitogenic kinases. When normal cells are protected, the selectivity and potency of multi-drug combinations can be further enhanced by adding synergistic drugs, in theory, eliminating the deadliest cancer clones with minimal side effects. I also discuss how the recent success of Trilaciclib may foster similar approaches into clinical practice, how to mitigate systemic side effects of chemotherapy in patients with brain tumors and how to ensure that protective drugs would only protect normal cells (not cancer cells) in a particular patient.
    MeSH term(s) Humans ; Drug Resistance, Neoplasm ; Antineoplastic Agents/pharmacology ; Brain Neoplasms ; Caspases ; Drug Combinations
    Chemical Substances Antineoplastic Agents ; Caspases (EC 3.4.22.-) ; Drug Combinations
    Language English
    Publishing date 2023-03-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.28382
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Cancer prevention with rapamycin.

    Blagosklonny, Mikhail V

    Oncotarget

    2023  Volume 14, Page(s) 342–350

    Abstract: Rapamycin (sirolimus) and other rapalogs (everolimus) are anti-cancer and anti-aging drugs, which delay cancer by directly targeting pre-cancerous cells and, indirectly, by slowing down organism aging. Cancer is an age-related disease and, figuratively, ... ...

    Abstract Rapamycin (sirolimus) and other rapalogs (everolimus) are anti-cancer and anti-aging drugs, which delay cancer by directly targeting pre-cancerous cells and, indirectly, by slowing down organism aging. Cancer is an age-related disease and, figuratively, by slowing down time (and aging), rapamycin may delay cancer. In several dozen murine models, rapamycin robustly and reproducibly prevents cancer. Rapamycin slows cell proliferation and tumor progression, thus delaying the onset of cancer in carcinogen-treated, genetically cancer-prone and normal mice. Data on the use of rapamycin and everolimus in organ-transplant patients are consistent with their cancer-preventive effects. Treatment with rapamycin was proposed to prevent lung cancer in smokers and former smokers. Clinical trials in high-risk populations are warranted.
    MeSH term(s) Mice ; Animals ; Sirolimus/pharmacology ; Sirolimus/therapeutic use ; Everolimus/pharmacology ; Aging ; Carcinogens/pharmacology ; Lung Neoplasms/chemically induced ; Lung Neoplasms/prevention & control ; Lung Neoplasms/drug therapy
    Chemical Substances Sirolimus (W36ZG6FT64) ; Everolimus (9HW64Q8G6G) ; Carcinogens
    Language English
    Publishing date 2023-04-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2560162-3
    ISSN 1949-2553 ; 1949-2553
    ISSN (online) 1949-2553
    ISSN 1949-2553
    DOI 10.18632/oncotarget.28410
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: As expected, based on rapamycin-like p53-mediated gerosuppression, mTOR inhibition acts as a checkpoint in p53-mediated tumor suppression.

    Blagosklonny, Mikhail V

    Oncoscience

    2022  Volume 9, Page(s) 38–41

    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article
    ISSN 2331-4737
    ISSN 2331-4737
    DOI 10.18632/oncoscience.561
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: As predicted by hyperfunction theory, rapamycin treatment during development extends lifespan.

    Blagosklonny, Mikhail V

    Aging

    2022  Volume 14, Issue 5, Page(s) 2020–2024

    MeSH term(s) Longevity ; Sirolimus/pharmacology ; Sirolimus/therapeutic use ; TOR Serine-Threonine Kinases
    Chemical Substances TOR Serine-Threonine Kinases (EC 2.7.11.1) ; Sirolimus (W36ZG6FT64)
    Language English
    Publishing date 2022-03-05
    Publishing country United States
    Document type Journal Article
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.203937
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Atlos Labs and the quest for immortality: but can we live longer right now?

    Blagosklonny, Mikhail V

    Oncoscience

    2022  Volume 9, Page(s) 13–16

    Abstract: Some visionaries prefer to dream of immortality rather than to actually live longer. Here I discuss how combining rapamycin with other modalities may let us live long enough to benefit from future discoveries in cellular reprogramming and what needs to ... ...

    Abstract Some visionaries prefer to dream of immortality rather than to actually live longer. Here I discuss how combining rapamycin with other modalities may let us live long enough to benefit from future discoveries in cellular reprogramming and what needs to be done at Atlos Labs to make this happen.
    Language English
    Publishing date 2022-04-22
    Publishing country United States
    Document type Journal Article
    ISSN 2331-4737
    ISSN 2331-4737
    DOI 10.18632/oncoscience.552
    Database MEDical Literature Analysis and Retrieval System OnLINE

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