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FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity (2023)
Journal Article
Fiorillo, M., Ricci, E., Fava, M., Longobucco, C., Sotgia, F., Rizza, P., …Sisci, D. (in press). FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity. Cells, 12(24), 2777. https://doi.org/10.3390/cells12242777

Tamoxifen-resistant breast cancer cells (TamR-BCCs) are characterized by an enhanced metabolic phenotype compared to tamoxifen-sensitive cells. FoxO3a is an important modulator of cell metabolism, and its deregulation has been involved in the acquisi... Read More about FoxO3a Drives the Metabolic Reprogramming in Tamoxifen-Resistant Breast Cancer Cells Restoring Tamoxifen Sensitivity.

High ATP production fuels cancer drug resistance and metastasis : implications for mitochondrial ATP depletion therapy (2021)
Journal Article
Fiorillo, M., Ozsvari, B., Sotgia, F., & Lisanti, M. (2021). High ATP production fuels cancer drug resistance and metastasis : implications for mitochondrial ATP depletion therapy. Frontiers in Oncology, 11, 740720. https://doi.org/10.3389/fonc.2021.740720

Recently, we presented evidence that high mitochondrial ATP production is a new therapeutic target for cancer treatment. Using ATP as a biomarker, we isolated the “metabolically fittest” cancer cells from the total cell population. Importantly, ATP-h... Read More about High ATP production fuels cancer drug resistance and metastasis : implications for mitochondrial ATP depletion therapy.

Mitochondrial Fission Factor (MFF) inhibits mitochondrial metabolism and reduces breast cancer stem cell (CSC) activity (2020)
Journal Article
Sánchez-Alvarez, R., De Francesco, E., Fiorillo, M., Sotgia, F., & Lisanti, M. (2020). Mitochondrial Fission Factor (MFF) inhibits mitochondrial metabolism and reduces breast cancer stem cell (CSC) activity. Frontiers in Oncology, 10, 1776. https://doi.org/10.3389/fonc.2020.01776

Elevated mitochondrial biogenesis and metabolism represent key features of breast cancer stem cells (CSCs), whose propagation is conducive to disease onset and progression. Therefore, interfering with mitochondria biology and function may be regarded... Read More about Mitochondrial Fission Factor (MFF) inhibits mitochondrial metabolism and reduces breast cancer stem cell (CSC) activity.

Deferiprone (DFP) targets cancer stem cell (CSC) propagation by inhibiting mitochondrial metabolism and inducing ROS production (2020)
Journal Article
Fiorillo, M., Tóth, F., Brindisi, M., Sotgia, F., & Lisanti, M. (2020). Deferiprone (DFP) targets cancer stem cell (CSC) propagation by inhibiting mitochondrial metabolism and inducing ROS production. Cells, 9(6), e1529. https://doi.org/10.3390/cells9061529

Deferiprone (DFP), also known as Ferriprox, is an FDA-approved, orally active, iron chelator that is currently used clinically for the treatment of iron-overload, especially in thalassaemia major. As iron is a critical factor in Fe-S cluster assembly... Read More about Deferiprone (DFP) targets cancer stem cell (CSC) propagation by inhibiting mitochondrial metabolism and inducing ROS production.

5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer (2020)
Journal Article
Armentano, B., Curcio, R., Brindisi, M., Mancuso, R., Rago, V., Ziccarelli, I., …Cappello, A. (2020). 5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer. Biomedicines, 8(2), e35. https://doi.org/10.3390/biomedicines8020035

Oxazolidinones are antibiotics that inhibit protein synthesis by binding the 50S ribosomal subunit. Recently, numerous worldwide researches focused on their properties and possible involvement in cancer therapy have been conducted. Here, we evaluated... Read More about 5-(carbamoylmethylene)-oxazolidin-2-ones as a promising class of heterocycles inducing apoptosis triggered by increased ROS levels and mitochondrial dysfunction in breast and cervical cancer.

FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer (2019)
Journal Article
Pellegrino, M., Rizza, P., Donà, A., Nigro, A., Ricci, E., Fiorillo, M., …Morelli, C. (2019). FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer. Cancers, 11(12), e1858. https://doi.org/10.3390/cancers11121858

Background: Resistance to endocrine treatments is a major clinical challenge in the management of estrogen receptor positive breast cancers. Although multiple mechanisms leading to endocrine resistance have been proposed, the poor outcome of this sub... Read More about FoxO3a as a positive prognostic marker and a therapeutic target in Tamoxifen-resistant breast cancer.

Thioalbamide, a thioamidated peptide from amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress (2019)
Journal Article
Frattaruolo, L., Fiorillo, M., Brindisi, M., Curcio, R., Dolce, V., Lacret, R., …Cappello, A. (2019). Thioalbamide, a thioamidated peptide from amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress. Cells, 8(11), e1408. https://doi.org/10.3390/cells8111408

Thioalbamide, a thioamidated peptide biosynthesized by Amycolatopsis alba, is a thioviridamide-like molecule, and is part of a family of natural products representing a focus of biotechnological and pharmaceutical research in recent years due to thei... Read More about Thioalbamide, a thioamidated peptide from amycolatopsis alba, affects tumor growth and stemness by inducing metabolic dysfunction and oxidative stress.

Doxycycline, Azithromycin and vitamin C (DAV) : a potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs) (2019)
Journal Article
Fiorillo, M., Tóth, F., Sotgia, F., & Lisanti, M. (2019). Doxycycline, Azithromycin and vitamin C (DAV) : a potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs). Aging, 11(8), 2202-2216. https://doi.org/10.18632/aging.101905

Here, we devised a new strategy for eradicating cancer stem cells (CSCs), via a "synthetic-metabolic" approach, involving two FDA-approved antibiotics and a dietary vitamin supplement. This approach was designed to induce a "rho-zero-like" phenotype... Read More about Doxycycline, Azithromycin and vitamin C (DAV) : a potent combination therapy for targeting mitochondria and eradicating cancer stem cells (CSCs).

Hallmarks of the cancer cell of origin : comparisons with "energetic" cancer stem cells (e-CSCs) (2019)
Journal Article
Sotgia, F., Fiorillo, M., & Lisanti, M. (2019). Hallmarks of the cancer cell of origin : comparisons with "energetic" cancer stem cells (e-CSCs). Aging, 11(3), 1065-1068. https://doi.org/10.18632/aging.101822

Here, we discuss the expected hallmark(s) of the cancer cell of origin and how this may be related to a new tumor cell phenotype, namely "energetic" cancer stem cells (e-CSCs). e-CSCs show many features that would be characteristic of the cancer cell... Read More about Hallmarks of the cancer cell of origin : comparisons with "energetic" cancer stem cells (e-CSCs).

“Energetic” cancer stem cells (e-CSCs) : a new hyper-metabolic and proliferative tumor cell phenotype, driven by mitochondrial energy (2019)
Journal Article
Fiorillo, M., Sotgia, F., & Lisanti, M. (2019). “Energetic” cancer stem cells (e-CSCs) : a new hyper-metabolic and proliferative tumor cell phenotype, driven by mitochondrial energy. Frontiers in Oncology, 8(677), https://doi.org/10.3389/fonc.2018.00677

Here, we provide the necessary evidence that mitochondrial metabolism drives the anchorage-independent proliferation of CSCs. Two human breast cancer cell lines, MCF7 [ER(+)] and MDA-MB-468 (triple-negative), were used as model systems. To
directly... Read More about “Energetic” cancer stem cells (e-CSCs) : a new hyper-metabolic and proliferative tumor cell phenotype, driven by mitochondrial energy.

The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling : implicating TIGAR in somatic resistance to endocrine therapy (2018)
Journal Article
Fiorillo, M., Sanchez-Alvarez, R., Sotgia, F., & Lisanti, M. (2018). The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling : implicating TIGAR in somatic resistance to endocrine therapy. Aging, 10(12), 4000-4023. https://doi.org/10.18632/aging.101690

Naturally-occurring somatic mutations in the estrogen receptor gene (ESR1) have been previously implicated in the clinical development of resistance to hormonal therapies, such as Tamoxifen. For example, the somatic mutation Y537S has been specifical... Read More about The ER-alpha mutation Y537S confers Tamoxifen-resistance via enhanced mitochondrial metabolism, glycolysis and Rho-GDI/PTEN signaling : implicating TIGAR in somatic resistance to endocrine therapy.

A mitochondrial based oncology platform for targeting cancer stem cells (CSCs) : MITO-ONC-RX (2018)
Journal Article
Sotgia, F., Ozsvari, B., Fiorillo, M., De Francesco, E., Bonuccelli, G., & Lisanti, M. (2018). A mitochondrial based oncology platform for targeting cancer stem cells (CSCs) : MITO-ONC-RX. Cell Cycle, 17(17), 2091-2100. https://doi.org/10.1080/15384101.2018.1515551

Here, we wish to propose a new systematic approach to cancer therapy, based on the targeting of mitochondrial metabolism, especially in cancer stem cells (CSCs). In the future, we envision that anti-mitochondrial therapy would ultimately be practiced... Read More about A mitochondrial based oncology platform for targeting cancer stem cells (CSCs) : MITO-ONC-RX.

Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism (2018)
Journal Article
Fiorillo, M., Peiris-Pagès, M., Sanchez-Alvarez, R., Bartella, L., Di Donna, L., Dolce, V., …Lisanti, M. (2018). Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism. BBA - Bioenergetics, 1859(9), 984-996. https://doi.org/10.1016/j.bbabio.2018.03.018

Here, we show that a 2:1 mixture of Brutieridin and Melitidin, termed “BMF”, has a statin-like properties, which
blocks the action of the rate-limiting enzyme for mevalonate biosynthesis, namely HMGR (3-hydroxy-3-methylglutaryl-
CoA-reductase). Mor... Read More about Bergamot natural products eradicate cancer stem cells (CSCs) by targeting mevalonate, Rho-GDI-signalling and mitochondrial metabolism.

Mitochondrial markers predict recurrence, metastasis and Tamoxifen-resistance in breast cancer patients : early detection of treatment failure with companion diagnostics (2017)
Journal Article
Sotgia, F., Fiorillo, M., & Lisanti, M. (2017). Mitochondrial markers predict recurrence, metastasis and Tamoxifen-resistance in breast cancer patients : early detection of treatment failure with companion diagnostics. Oncotarget, 2017(8), 68730-68745. https://doi.org/10.18632/oncotarget.19612

Here, we used a data-mining and informatics approach to discover new biomarkers of resistance to hormonal therapy in breast cancer. More specifically, we investigated whether nuclear-encoded genes associated with mitochondrial biogenesis can be used... Read More about Mitochondrial markers predict recurrence, metastasis and Tamoxifen-resistance in breast cancer patients : early detection of treatment failure with companion diagnostics.

Mitoriboscins : mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast (2017)
Journal Article
Ozsvari, B., Fiorillo, M., Bonuccelli, G., Cappello, A., Frattaruolo, L., Sotgia, F., …Lisanti, M. (2017). Mitoriboscins : mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast. Oncotarget, 2017(8), 67457-67472. https://doi.org/10.18632/oncotarget.19084

The “endo-symbiotic theory of mitochondrial evolution” states that mitochondrial organelles evolved from engulfed aerobic bacteria, after millions of years of symbiosis and adaptation. Here, we have exploited this premise to design new antibiotics an... Read More about Mitoriboscins : mitochondrial-based therapeutics targeting cancer stem cells (CSCs), bacteria and pathogenic yeast.

Mitochondrial “power” drives tamoxifen resistance : NQO1 and GCLC are new therapeutic targets in breast cancer (2017)
Journal Article
Fiorillo, M., Sotgia, F., Sisci, D., Cappello, A., & Lisanti, M. (2017). Mitochondrial “power” drives tamoxifen resistance : NQO1 and GCLC are new therapeutic targets in breast cancer. Oncotarget, 2017(8), 20309-20327. https://doi.org/10.18632/oncotarget.15852

Here, we identified two new molecular targets, which are functionally sufficient
to metabolically confer the tamoxifen-resistance phenotype in human breast cancer
cells. Briefly, ~20 proteins were first selected as potential candidates, based on
u... Read More about Mitochondrial “power” drives tamoxifen resistance : NQO1 and GCLC are new therapeutic targets in breast cancer.