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Article ; Online: The thiosemicarbazone, DpC, broadly synergizes with multiple anti-cancer therapeutics and demonstrates temperature- and energy-dependent uptake by tumor cells.

Dharmasivam, Mahendiran / Azad, Mahan Gholam / Afroz, Rizwana / Richardson, Vera / Jansson, Patric J / Richardson, Des R

Biochimica et biophysica acta. General subjects

2022 Volume 1866, Issue 8, Page(s) 130152

Abstract: Background: The di-2-pyridylketone thiosemicarbazones, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), demonstrate potent and selective anti-tumor activity. In fact, ... ...

Abstract	Background: The di-2-pyridylketone thiosemicarbazones, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), demonstrate potent and selective anti-tumor activity. In fact, DpC entered Phase I clinical trials for advanced and resistant tumors. Methods: This investigation examined the activity of these thiosemicarbazones in five tumor cell-types compared to nine clinically used chemotherapeutics and also in combination with these drugs. Results: Dp44mT and especially DpC demonstrated potent anti-proliferative activity that was significantly greater than a range of standard anti-cancer therapeutics. As most anti-cancer drugs are given in combination, further studies were performed to examine the synergistic activity of DpC or Dp44mT with these chemotherapeutics. Combination experiments revealed broad synergy between Dp44mT or DpC upon addition of these drugs, with a sequential protocol of treating first with standard chemotherapies followed by incubation with the thiosemicarbazones being optimal. However, combining DpC and Dp44mT resulted in a pronounced antagonistic drug interaction. To dissect the mechanism of this latter effect, custom-prepared Conclusions and general significance: These studies demonstrate the potent and broad anti-proliferative activity of Dp44mT and particularly DpC, and are important for establishing optimized combinations with standard chemotherapies.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Biological Transport ; Cell Line, Tumor ; Temperature ; Thiosemicarbazones/pharmacology
Chemical Substances	Antineoplastic Agents ; Thiosemicarbazones
Language	English
Publishing date	2022-04-15
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1872-8006 ; 1879-2596 ; 1879-260X ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbagen.2022.130152
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Article ; Online: Mitoribosomal synthetic lethality overcomes multidrug resistance in MYC-driven neuroblastoma.

Borankova, Karolina / Krchniakova, Maria / Leck, Lionel Y W / Kubistova, Adela / Neradil, Jakub / Jansson, Patric J / Hogarty, Michael D / Skoda, Jan

Cell death & disease

2023 Volume 14, Issue 11, Page(s) 747

Abstract: Mitochondria are central for cancer responses to therapy-induced stress signals. Refractory tumors often show attenuated sensitivity to apoptotic signaling, yet clinically relevant molecular actors to target mitochondria-mediated resistance remain ... ...

Abstract	Mitochondria are central for cancer responses to therapy-induced stress signals. Refractory tumors often show attenuated sensitivity to apoptotic signaling, yet clinically relevant molecular actors to target mitochondria-mediated resistance remain elusive. Here, we show that MYC-driven neuroblastoma cells rely on intact mitochondrial ribosome (mitoribosome) processivity and undergo cell death following pharmacological inhibition of mitochondrial translation, regardless of their multidrug/mitochondrial resistance and stem-like phenotypes. Mechanistically, inhibiting mitoribosomes induced the mitochondrial stress-activated integrated stress response (ISR), leading to downregulation of c-MYC/N-MYC proteins prior to neuroblastoma cell death, which could be both rescued by the ISR inhibitor ISRIB. The ISR blocks global protein synthesis and shifted the c-MYC/N-MYC turnover toward proteasomal degradation. Comparing models of various neuroectodermal tumors and normal fibroblasts revealed overexpression of MYC proteins phosphorylated at the degradation-promoting site T58 as a factor that predetermines vulnerability of MYC-driven neuroblastoma to mitoribosome inhibition. Reducing N-MYC levels in a neuroblastoma model with tunable MYCN expression mitigated cell death induction upon inhibition of mitochondrial translation and functionally validated the propensity of neuroblastoma cells for MYC-dependent cell death in response to the mitochondrial ISR. Notably, neuroblastoma cells failed to develop significant resistance to the mitoribosomal inhibitor doxycycline over a long-term repeated (pulsed) selection. Collectively, we identify mitochondrial translation machinery as a novel synthetic lethality target for multidrug-resistant MYC-driven tumors.
MeSH term(s)	Humans ; Synthetic Lethal Mutations ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Apoptosis ; Signal Transduction ; Neuroblastoma/drug therapy ; Neuroblastoma/genetics ; Neuroblastoma/metabolism ; N-Myc Proto-Oncogene Protein/genetics ; N-Myc Proto-Oncogene Protein/metabolism ; Cell Line, Tumor
Chemical Substances	Proto-Oncogene Proteins c-myc ; N-Myc Proto-Oncogene Protein
Language	English
Publishing date	2023-11-16
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-023-06278-x
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Article: The thiosemicarbazone, DpC, broadly synergizes with multiple anti-cancer therapeutics and demonstrates temperature- and energy-dependent uptake by tumor cells

Dharmasivam, Mahendiran / Azad, Mahan Gholam / Afroz, Rizwana / Richardson, Vera / Jansson, Patric J. / Richardson, Des R.

Biochimica et biophysica acta. 2022 Apr. 11,

2022

Abstract: The di-2-pyridylketone thiosemicarbazones, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), demonstrate potent and selective anti-tumor activity. In fact, DpC entered ... ...

Abstract	The di-2-pyridylketone thiosemicarbazones, di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) and di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC), demonstrate potent and selective anti-tumor activity. In fact, DpC entered Phase I clinical trials for advanced and resistant tumors. This investigation examined the activity of these thiosemicarbazones in five tumor cell-types compared to nine clinically used chemotherapeutics and also in combination with these drugs. Dp44mT and especially DpC demonstrated potent anti-proliferative activity that was significantly greater than a range of standard anti-cancer therapeutics. As most anti-cancer drugs are given in combination, further studies were performed to examine the synergistic activity of DpC or Dp44mT with these chemotherapeutics. Combination experiments revealed broad synergy between Dp44mT or DpC upon addition of these drugs, with a sequential protocol of treating first with standard chemotherapies followed by incubation with the thiosemicarbazones being optimal. However, combining DpC and Dp44mT resulted in a pronounced antagonistic drug interaction. To dissect the mechanism of this latter effect, custom-prepared ¹⁴C-DpC was implemented and examined for its uptake by cells. The avid uptake of ¹⁴C-DpC by tumor cells observed at 37 °C was suppressed at 4 °C and by the metabolic inhibitor, sodium fluoride, suggesting a temperature- and energy-dependent mechanism. Furthermore, competition studies using an excess of unlabeled Dp44mT or DpC inhibited ¹⁴C-DpC or ¹⁴C-Dp44mT uptake, respectively, suggesting these ligands utilize the same carrier/receptor, antagonizing the internalization of each other. These studies demonstrate the potent and broad anti-proliferative activity of Dp44mT and particularly DpC, and are important for establishing optimized combinations with standard chemotherapies.
Keywords	antineoplastic activity ; cancer therapy ; drug interactions ; drug therapy ; ligands ; neoplasms ; sodium fluoride ; synergism
Language	English
Dates of publication	2022-0411
Publishing place	Elsevier B.V.
Document type	Article
Note	Pre-press version
ZDB-ID	840755-1
ISSN	0304-4165
ISSN	0304-4165
DOI	10.1016/j.bbagen.2022.130152
Database	NAL-Catalogue (AGRICOLA)

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Article: Tumour Microenvironment Stress Promotes the Development of Drug Resistance

Seebacher, Nicole A. / Krchniakova, Maria / Stacy, Alexandra E. / Skoda, Jan / Jansson, Patric J.

Antioxidants. 2021 Nov. 11, v. 10, no. 11

2021

Abstract: Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but ... ...

Abstract	Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells.
Keywords	apoptosis ; autophagy ; cancer therapy ; cell viability ; death ; drug development ; drug therapy ; drugs ; metastasis ; multiple drug resistance ; neoplasm cells ; neoplasm progression ; neoplasms ; phenotype ; reactive oxygen species ; stem cells
Language	English
Dates of publication	2021-1111
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10111801
Database	NAL-Catalogue (AGRICOLA)

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Article: Emerging Role of Autophagy in the Development and Progression of Oral Squamous Cell Carcinoma.

Abd El-Aziz, Yomna S / Leck, Lionel Y W / Jansson, Patric J / Sahni, Sumit

Cancers

2021 Volume 13, Issue 24

Abstract: Autophagy is a cellular catabolic process, which is characterized by degradation of damaged proteins and organelles needed to supply the cell with essential nutrients. At basal levels, autophagy is important to maintain cellular homeostasis and ... ...

Abstract	Autophagy is a cellular catabolic process, which is characterized by degradation of damaged proteins and organelles needed to supply the cell with essential nutrients. At basal levels, autophagy is important to maintain cellular homeostasis and development. It is also a stress responsive process that allows the cells to survive when subjected to stressful conditions such as nutrient deprivation. Autophagy has been implicated in many pathologies including cancer. It is well established that autophagy plays a dual role in different cancer types. There is emerging role of autophagy in oral squamous cell carcinoma (OSCC) development and progression. This review will focus on the role played by autophagy in relation to different aspects of cancer progression and discuss recent studies exploring the role of autophagy in OSCC. It will further discuss potential therapeutic approaches to target autophagy in OSCC.
Language	English
Publishing date	2021-12-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13246152
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Article: Tumour Microenvironment Stress Promotes the Development of Drug Resistance.

Seebacher, Nicole A / Krchniakova, Maria / Stacy, Alexandra E / Skoda, Jan / Jansson, Patric J

Antioxidants (Basel, Switzerland)

2021 Volume 10, Issue 11

Abstract	Multi-drug resistance (MDR) is a leading cause of cancer-related death, and it continues to be a major barrier to cancer treatment. The tumour microenvironment (TME) has proven to play an essential role in not only cancer progression and metastasis, but also the development of resistance to chemotherapy. Despite the significant advances in the efficacy of anti-cancer therapies, the development of drug resistance remains a major impediment to therapeutic success. This review highlights the interplay between various factors within the TME that collectively initiate or propagate MDR. The key TME-mediated mechanisms of MDR regulation that will be discussed herein include (1) altered metabolic processing and the reactive oxygen species (ROS)-hypoxia inducible factor (HIF) axis; (2) changes in stromal cells; (3) increased cancer cell survival via autophagy and failure of apoptosis; (4) altered drug delivery, uptake, or efflux and (5) the induction of a cancer stem cell (CSC) phenotype. The review also discusses thought-provoking ideas that may assist in overcoming the TME-induced MDR. We conclude that stressors from the TME and exposure to chemotherapeutic agents are strongly linked to the development of MDR in cancer cells. Therefore, there remains a vast area for potential research to further elicit the interplay between factors existing both within and outside the TME. Elucidating the mechanisms within this network is essential for developing new therapeutic strategies that are less prone to failure due to the development of resistance in cancer cells.
Language	English
Publishing date	2021-11-11
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10111801
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Article ; Online: Role of ABCB1 in mediating chemoresistance of triple-negative breast cancers.

Abd El-Aziz, Yomna S / Spillane, Andrew J / Jansson, Patric J / Sahni, Sumit

Bioscience reports

2021 Volume 41, Issue 2

Abstract: Triple-negative breast cancer (TNBC) is a group of breast cancers which neither express hormonal receptors nor human epidermal growth factor receptor. Hence, there is a lack of currently known targeted therapies and the only available line of systemic ... ...

Abstract	Triple-negative breast cancer (TNBC) is a group of breast cancers which neither express hormonal receptors nor human epidermal growth factor receptor. Hence, there is a lack of currently known targeted therapies and the only available line of systemic treatment option is chemotherapy or more recently immune therapy. However, in patients with relapsed disease after adjuvant or neoadjuvant therapy, resistance to chemotherapeutic agents has often developed, which results in poor treatment response. Multidrug resistance (MDR) has emerged as an important mechanism by which TNBCs mediate drug resistance and occurs primarily due to overexpression of ATP-binding cassette (ABC) transporter proteins such as P-glycoprotein (Pgp). Pgp overexpression had been linked to poor outcome, reduced survival rates and chemoresistance in patients. The aim of this mini-review is to provide a topical overview of the recent studies and to generate further interest in this critical research area, with the aim to develop an effective and safe approach for overcoming Pgp-mediated chemoresistance in TNBC.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B/physiology ; Drug Resistance, Neoplasm/physiology ; Humans ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology
Chemical Substances	ABCB1 protein, human ; ATP Binding Cassette Transporter, Subfamily B
Language	English
Publishing date	2021-02-04
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	764946-0
ISSN	1573-4935 ; 0144-8463
ISSN (online)	1573-4935
ISSN	0144-8463
DOI	10.1042/BSR20204092
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Article ; Online: Autophagy: A promising target for triple negative breast cancers.

Abd El-Aziz, Yomna S / Gillson, Josef / Jansson, Patric J / Sahni, Sumit

Pharmacological research

2021 Volume 175, Page(s) 106006

Abstract: Triple negative breast cancer (TNBC) is the most aggressive type of breast cancers which constitutes about 15% of all breast cancer cases and characterized by negative expression of hormonal receptors and human epidermal growth factor receptor 2 (HER2). ... ...

Abstract	Triple negative breast cancer (TNBC) is the most aggressive type of breast cancers which constitutes about 15% of all breast cancer cases and characterized by negative expression of hormonal receptors and human epidermal growth factor receptor 2 (HER2). Thus, endocrine and HER2 targeted therapies are not effective toward TNBCs, and they mainly rely on chemotherapy and surgery for treatment. Despite recent advances in chemotherapy, 40% of TNBC patients develop a metastatic relapse and recurrence. Therefore, understanding the molecular profile of TNBC is warranted to identify targets that can be selected for the development of a new and effective therapeutic approach. Autophagy is an internal defensive mechanism that allows the cells to survive under different stressors. It has been well known that autophagy exerts a crucial role in cancer progression. The critical role of autophagy in TNBC progression is emerging in recent years. This review will discuss autophagic pathway, how autophagy affects TNBC progression and recent therapeutic approaches that can target autophagy as a new treatment modality.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Autophagy/drug effects ; Female ; Humans ; Triple Negative Breast Neoplasms/drug therapy
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2021-11-27
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1003347-6
ISSN	1096-1186 ; 0031-6989 ; 1043-6618
ISSN (online)	1096-1186
ISSN	0031-6989 ; 1043-6618
DOI	10.1016/j.phrs.2021.106006
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Zs.A 721: Show issues

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Article ; Online: Targeting Wnt/tenascin C-mediated cross talk between pancreatic cancer cells and stellate cells via activation of the metastasis suppressor NDRG1.

Geleta, Bekesho / Tout, Faten S / Lim, Syer Choon / Sahni, Sumit / Jansson, Patric J / Apte, Minoti V / Richardson, Des R / Kovačević, Žaklina

The Journal of biological chemistry

2022 Volume 298, Issue 3, Page(s) 101608

Abstract: A major barrier to successful pancreatic cancer (PC) treatment is the surrounding stroma, which secretes growth factors/cytokines that promote PC progression. Wnt and tenascin C (TnC) are key ligands secreted by stromal pancreatic stellate cells (PSCs) ... ...

Abstract	A major barrier to successful pancreatic cancer (PC) treatment is the surrounding stroma, which secretes growth factors/cytokines that promote PC progression. Wnt and tenascin C (TnC) are key ligands secreted by stromal pancreatic stellate cells (PSCs) that then act on PC cells in a paracrine manner to activate the oncogenic β-catenin and YAP/TAZ signaling pathways. Therefore, therapies targeting oncogenic Wnt/TnC cross talk between PC cells and PSCs constitute a promising new therapeutic approach for PC treatment. The metastasis suppressor N-myc downstream-regulated gene-1 (NDRG1) inhibits tumor progression and metastasis in numerous cancers, including PC. We demonstrate herein that targeting NDRG1 using the clinically trialed anticancer agent di-2-pyridylketone-4-cyclohexyl-4-methyl-3-thiosemicarbazone (DpC) inhibited Wnt/TnC-mediated interactions between PC cells and the surrounding PSCs. Mechanistically, NDRG1 and DpC markedly inhibit secretion of Wnt3a and TnC by PSCs, while also attenuating Wnt/β-catenin and YAP/TAZ activation and downstream signaling in PC cells. This antioncogenic activity was mediated by direct inhibition of β-catenin and YAP/TAZ nuclear localization and by increasing the Wnt inhibitor, DKK1. Expression of NDRG1 also inhibited transforming growth factor (TGF)-β secretion by PC cells, a key mechanism by which PC cells activate PSCs. Using an in vivo orthotopic PC mouse model, we show DpC downregulated β-catenin, TnC, and YAP/TAZ, while potently increasing NDRG1 expression in PC tumors. We conclude that NDRG1 and DpC inhibit Wnt/TnC-mediated interactions between PC cells and PSCs. These results further illuminate the antioncogenic mechanism of NDRG1 and the potential of targeting this metastasis suppressor to overcome the oncogenic effects of the PC-PSC interaction.
MeSH term(s)	Animals ; Cell Communication ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; Neoplasm Metastasis ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Pancreatic Stellate Cells/metabolism ; Pancreatic Stellate Cells/pathology ; Tenascin/genetics ; Tenascin/metabolism ; beta Catenin/genetics ; beta Catenin/metabolism ; Pancreatic Neoplasms
Chemical Substances	CTNNB1 protein, mouse ; Cell Cycle Proteins ; Intracellular Signaling Peptides and Proteins ; N-myc downstream-regulated gene 1 protein ; Tenascin ; Tnc protein, mouse ; beta Catenin
Language	English
Publishing date	2022-01-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2022.101608
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Article ; Online: Novel combinatorial autophagy inhibition therapy for triple negative breast cancers.

Abd El-Aziz, Yomna S / Toit-Thompson, Taymin du / McKay, Matthew J / Molloy, Mark P / Stoner, Shihani / McDowell, Betty / Moon, Elizabeth / Sioson, Loretta / Sheen, Amy / Chou, Angela / Gill, Anthony J / Jansson, Patric J / Sahni, Sumit

European journal of pharmacology

2024 Volume 973, Page(s) 176568

Abstract: Background: Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer subtypes. It is characterized by lack of estrogen, progesterone and human epidermal growth factor 2 receptors, and thus, have limited therapeutic options. ... ...

Abstract	Background: Triple negative breast cancer (TNBC) has the worst prognosis among breast cancer subtypes. It is characterized by lack of estrogen, progesterone and human epidermal growth factor 2 receptors, and thus, have limited therapeutic options. Autophagy has been found to be correlated with poor prognosis and aggressive behaviour in TNBC. This study aimed to target autophagy in TNBC via a novel approach to inhibit TNBC progression. Methods: Immunoblotting and confocal microscopy were carried out to examine the effect of tumor microenvironmental stressors on autophagy. Cellular proliferation and migration assays were used to test the effect of different autophagy inhibitors and standard chemotherapy alone or in combination. In vivo xenograft mouse model was utilized to assess the effect of autophagy inhibitors alone or in combination with Paclitaxel. High resolution mass spectrometry based proteomic analysis was performed to explore the mechanisms behind chemoresistance in TNBC. Lastly, immunohistochemistry was done to assess the correlation between autophagy related proteins and clinical characteristics in TNBC tissue specimens. Results: Metabolic stressors were found to induce autophagy in TNBC cell lines. Autophagy initiation inhibitors, SAR405 and MRT68921, showed marked synergy in their anti-proliferative activity in both chemosensitive and chemoresistant TNBC cell models. Paradoxically, positive expression of autophagosome marker LC3 was shown to be associated with better overall survival of TNBC patients. Conclusion: In this study, a novel combination between different autophagy inhibitors was identified which inhibited tumor cell proliferation in both chemosensitive and chemoresistant TNBC cells and could result in development of a novel treatment modality against TNBC.
Language	English
Publishing date	2024-04-09
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	80121-5
ISSN	1879-0712 ; 0014-2999
ISSN (online)	1879-0712
ISSN	0014-2999
DOI	10.1016/j.ejphar.2024.176568
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