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Article ; Online: HER3 in cancer: from the bench to the bedside.

Gandullo-Sánchez, Lucía / Ocaña, Alberto / Pandiella, Atanasio

Journal of experimental & clinical cancer research : CR

2022 Volume 41, Issue 1, Page(s) 310

Abstract: The HER3 protein, that belongs to the ErbB/HER receptor tyrosine kinase (RTK) family, is expressed in several types of tumors. That fact, together with the role of HER3 in promoting cell proliferation, implicate that targeting HER3 may have therapeutic ... ...

Abstract	The HER3 protein, that belongs to the ErbB/HER receptor tyrosine kinase (RTK) family, is expressed in several types of tumors. That fact, together with the role of HER3 in promoting cell proliferation, implicate that targeting HER3 may have therapeutic relevance. Furthermore, expression and activation of HER3 has been linked to resistance to drugs that target other HER receptors such as agents that act on EGFR or HER2. In addition, HER3 has been associated to resistance to some chemotherapeutic drugs. Because of those circumstances, efforts to develop and test agents targeting HER3 have been carried out. Two types of agents targeting HER3 have been developed. The most abundant are antibodies or engineered antibody derivatives that specifically recognize the extracellular region of HER3. In addition, the use of aptamers specifically interacting with HER3, vaccines or HER3-targeting siRNAs have also been developed. Here we discuss the state of the art of the preclinical and clinical development of drugs aimed at targeting HER3 with therapeutic purposes.
MeSH term(s)	Humans ; Cell Line, Tumor ; Cell Proliferation ; Neoplasms/drug therapy ; Neoplasms/genetics ; Receptor, ErbB-2/genetics ; Receptor, ErbB-2/metabolism ; Receptor, ErbB-3/genetics ; Receptor, ErbB-3/metabolism
Chemical Substances	Receptor, ErbB-2 (EC 2.7.10.1) ; Receptor, ErbB-3 (EC 2.7.10.1)
Language	English
Publishing date	2022-10-21
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-022-02515-x
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Article ; Online: Proteolysis targeting chimeras (PROTACs) in cancer therapy.

Ocaña, Alberto / Pandiella, Atanasio

Journal of experimental & clinical cancer research : CR

2020 Volume 39, Issue 1, Page(s) 189

Abstract: Exploitation of the protein degradation machinery as a therapeutic strategy to degrade oncogenic proteins is experiencing revolutionary advances with the development of proteolysis targeting chimeras (PROTACs). PROTACs are heterobifunctional structures ... ...

Abstract	Exploitation of the protein degradation machinery as a therapeutic strategy to degrade oncogenic proteins is experiencing revolutionary advances with the development of proteolysis targeting chimeras (PROTACs). PROTACs are heterobifunctional structures consisting of a ligand that binds a protein to be degraded and a ligand for an E3 ubiquitin ligase. The bridging between the protein of interest and the E3 ligase mediated by the PROTAC facilitates ubiquitination of the protein and its proteasomal degradation. In this review we discuss the molecular medicine behind PROTAC mechanism of action, with special emphasis on recent developments and their potential translation to the clinical setting.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Humans ; Molecular Targeted Therapy ; Neoplasm Proteins/antagonists & inhibitors ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Proteolysis/drug effects ; Ubiquitination
Chemical Substances	Antineoplastic Agents ; Neoplasm Proteins
Language	English
Publishing date	2020-09-15
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-020-01672-1
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Article: Antibody-Drug Conjugates: A Promising Novel Therapy for the Treatment of Ovarian Cancer.

Manzano, Aranzazu / Ocaña, Alberto

Cancers

2020 Volume 12, Issue 8

Abstract: Antibody-drug conjugates (ADCs) represent a novel and promising therapeutic strategy for the treatment of cancer patients. ADCs target antigens highly expressed on the membrane surface of tumor cells to selectively deliver a cytotoxic drug. Ovarian ... ...

Abstract	Antibody-drug conjugates (ADCs) represent a novel and promising therapeutic strategy for the treatment of cancer patients. ADCs target antigens highly expressed on the membrane surface of tumor cells to selectively deliver a cytotoxic drug. Ovarian tumors differentially express tumor-specific antigens, which can be used to guide ADCs. This strategy allows for optimizing tumor targeting while minimizing systemic toxicity compared to classical chemotherapeutic agents. ADCs can be improved by using a cleavable linker allowing the delivery of the toxic payload in surrounding cells not expressing the target protein, therefore acting on heterogeneous tumors with different cell populations. Currently, more than 15 ADCs are under preclinical investigation in ovarian cancer, and some of them have already been tested in early-phase clinical trials with promising results. In this review, we summarize the mechanism of action and the toxicity profile of ADCs and discuss the latest preclinical discoveries and forthcoming applications in ovarian cancer.
Language	English
Publishing date	2020-08-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12082223
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Article ; Online: Evaluation of heteroscorpionate ligands as scaffolds for the generation of Ruthenium(II) metallodrugs in breast cancer therapy.

Domínguez-Jurado, Elena / Ripoll, Consuelo / Lara-Sánchez, Agustín / Ocaña, Alberto / Vitórica-Yrezábal, Iñigo J / Bravo, Iván / Alonso-Moreno, Carlos

Journal of inorganic biochemistry

2024 Volume 253, Page(s) 112486

Abstract: The modular synthesis of the heteroscorpionate core is explored as a tool for the rapid development of ruthenium-based therapeutic agents. Starting with a series of structurally diverse alcohol-NN ligands, a family of heteroscorpionate-based ruthenium ... ...

Abstract	The modular synthesis of the heteroscorpionate core is explored as a tool for the rapid development of ruthenium-based therapeutic agents. Starting with a series of structurally diverse alcohol-NN ligands, a family of heteroscorpionate-based ruthenium derivatives was synthesized, characterized, and evaluated as an alternative to platinum therapy for breast cancer therapy. In vitro, the antitumoral activity of the novel derivatives was assessed in a series of breast cancer cell lines using UNICAM-1 and cisplatin as metallodrug control. Through this approach, a bimetallic heteroscorpionate-based metallodrug (RUSCO-2) was identified as the lead compound of the series with an IC
MeSH term(s)	Humans ; Female ; Breast Neoplasms/drug therapy ; Ruthenium/pharmacology ; Ruthenium/therapeutic use ; Ligands ; Chlorides ; Antineoplastic Agents ; MCF-7 Cells ; Coordination Complexes ; Cell Line, Tumor
Chemical Substances	Ruthenium (7UI0TKC3U5) ; Ligands ; Chlorides ; Antineoplastic Agents ; Coordination Complexes
Language	English
Publishing date	2024-01-18
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	162843-4
ISSN	1873-3344 ; 0162-0134
ISSN (online)	1873-3344
ISSN	0162-0134
DOI	10.1016/j.jinorgbio.2024.112486
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Article: Generation of Antibody-Drug Conjugate Resistant Models.

Gandullo-Sánchez, Lucía / Ocaña, Alberto / Pandiella, Atanasio

Cancers

2021 Volume 13, Issue 18

Abstract: In the last 20 years, antibody-drug conjugates (ADCs) have been incorporated into the oncology clinic as treatments for several types of cancer. So far, the Food and Drug Administration (FDA) has approved 11 ADCs and other ADCs are in the late stages of ... ...

Abstract	In the last 20 years, antibody-drug conjugates (ADCs) have been incorporated into the oncology clinic as treatments for several types of cancer. So far, the Food and Drug Administration (FDA) has approved 11 ADCs and other ADCs are in the late stages of clinical development. Despite the efficacy of this type of drug, the tumors of some patients may result in resistance to ADCs. Due to this, it is essential not only to comprehend resistance mechanisms but also to develop strategies to overcome resistance to ADCs. To reach these goals, the generation and use of preclinical models to study those mechanisms of resistance are critical. Some cells or patient tumors may result in primary resistance to the action of an ADC, even if they express the antigen against which the ADC is directed. Isolated primary tumoral cells, cell lines, or patient explants (patient-derived xenografts) with these characteristics can be used to study primary resistance. The most common method to generate models of secondary resistance is to treat cancer cell lines or tumors with an ADC. Two strategies, either continuous treatment with the ADC or intermittent treatment, have successfully been used to develop those resistance models.
Language	English
Publishing date	2021-09-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13184631
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Article: Using indirect methods to estimate population parameters of the Atlantic ghost crab from beaches in Northeastern Cuba

Ocaña, Frank A / de Jesús-Navarrete, Alberto

Regional studies in marine science. 2021 Mar., v. 43

2021

Abstract: Sandy beaches are dynamic systems that harbor diverse macrofauna species, such as the ghost crab Ocypode quadrata, which has a wide distribution and it is considered useful in ecological evaluations. Population parameters of O. quadrata based on indirect ...

Abstract	Sandy beaches are dynamic systems that harbor diverse macrofauna species, such as the ghost crab Ocypode quadrata, which has a wide distribution and it is considered useful in ecological evaluations. Population parameters of O. quadrata based on indirect methods were assessed at four tourist sandy beaches at northeastern Cuba from September 2010 to August 2011. Monthly samplings were carried out early in the morning. At each beach, five cross-shore transects were set at 50–60 m intervals, and consecutively 2x2 m quadrats were set from the upper swash level to the landward edge. Active burrows were counted and measured to the nearest millimeter using a caliper. Burrow density showed differences among beaches and a negative relation to the number of visitors. Burrow size showed differences among beaches as well as a positive relation to temperature, and non-significant relations to salinity and number of visitors. Burrow size frequency distribution showed a unimodal pattern skewed toward smaller sizes at the four beaches. Growth rates ranged from 0.57–1.4 year−1 and the growth performance was high (Φ′>3) at the four beaches. Growth performance was compared with other ocypodid populations (Uca spp., O. quadrata and Ucides spp.) inhabiting tropical coastal ecosystems using an auximetric plot. All ocypodid populations clustered forming one single ellipsoid in the auximetric plot supporting the use of borrows count and size as a reliable, non-invasive method to estimate population dynamics of this indicator species.
Keywords	Uca ; burrows ; crabs ; fauna ; frequency distribution ; growth performance ; indicator species ; marine science ; population dynamics ; salinity ; temperature ; tourists ; Cuba
Language	English
Dates of publication	2021-03
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ISSN	2352-4855
DOI	10.1016/j.rsma.2021.101705
Database	NAL-Catalogue (AGRICOLA)

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Article: Macrophage Cell Membrane Coating on Piperine-Loaded MIL-100(Fe) Nanoparticles for Breast Cancer Treatment.

Quijia, Christian Rafael / Navegante, Geovana / Sábio, Rafael Miguel / Valente, Valeria / Ocaña, Alberto / Alonso-Moreno, Carlos / Frem, Regina Célia Galvão / Chorilli, Marlus

Journal of functional biomaterials

2023 Volume 14, Issue 6

Abstract: Piperine (PIP), a compound found ... ...

Abstract	Piperine (PIP), a compound found in
Language	English
Publishing date	2023-06-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2648525-4
ISSN	2079-4983
ISSN	2079-4983
DOI	10.3390/jfb14060319
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Article ; Online: HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates.

Ocaña, Alberto / Amir, Eitan / Pandiella, Atanasio

Breast cancer research : BCR

2020 Volume 22, Issue 1, Page(s) 15

Abstract: Background: There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1).: Methods: Through a ... ...

Abstract	Background: There has been substantial interest in HER2 intratumoral heterogeneity as an explanation for the development of resistance to anti-HER2 therapies in breast cancer, particularly to trastuzumab emtansine (T-DM1). Methods: Through a literature-based approach, we discuss mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer. Results: We describe results from clinical studies reporting the effect of anti-HER2 strategies particularly ADCs and their mechanistic effect. We review biological findings underlying HER2 heterogeneity and its implication in the development of novel anti-HER2 drugs including new ADCs in clinical development like trastuzumab deruxtecan (DS-8201). Conclusions: We suggest potential mechanisms to optimize these compounds and their future clinical implementation.
MeSH term(s)	Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Clonal Evolution ; Drug Resistance, Neoplasm ; Female ; Humans ; Immunoconjugates/therapeutic use ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/metabolism
Chemical Substances	Immunoconjugates ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
Language	English
Publishing date	2020-01-31
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2015059-3
ISSN	1465-542X ; 1465-5411
ISSN (online)	1465-542X
ISSN	1465-5411
DOI	10.1186/s13058-020-1252-7
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Article: Novel ADCs and Strategies to Overcome Resistance to Anti-HER2 ADCs.

Díaz-Rodríguez, Elena / Gandullo-Sánchez, Lucía / Ocaña, Alberto / Pandiella, Atanasio

Cancers

2021 Volume 14, Issue 1

Abstract: During recent years, a number of new compounds against HER2 have reached clinics, improving the prognosis and quality of life of HER2-positive breast cancer patients. Nonetheless, resistance to standard-of-care drugs has motivated the development of ... ...

Abstract	During recent years, a number of new compounds against HER2 have reached clinics, improving the prognosis and quality of life of HER2-positive breast cancer patients. Nonetheless, resistance to standard-of-care drugs has motivated the development of novel agents, such as new antibody-drug conjugates (ADCs). The latter are a group of drugs that benefit from the potency of cytotoxic agents whose action is specifically guided to the tumor by the target-specific antibody. Two anti-HER2 ADCs have reached the clinic: trastuzumab-emtansine and, more recently, trastuzumab-deruxtecan. In addition, several other HER2-targeted ADCs are in preclinical or clinical development, some of them with promising signs of activity. In the present review, the structure, mechanism of action, and potential resistance to all these ADCs will be described. Specific attention will be given to discussing novel strategies to circumvent resistance to ADCs.
Language	English
Publishing date	2021-12-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14010154
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Article ; Online: Trastuzumab Emtansine: Mechanisms of Action and Resistance, Clinical Progress, and Beyond.

García-Alonso, Sara / Ocaña, Alberto / Pandiella, Atanasio

Trends in cancer

2020 Volume 6, Issue 2, Page(s) 130–146

Abstract: The approval of ado-trastuzumab emtansine (T-DM1) for clinical use represented a turning point both in HER2-positive breast cancer treatment and antibody-drug conjugate (ADC) technology. T-DM1 has proved its value and effectiveness in advanced metastatic ...

Abstract	The approval of ado-trastuzumab emtansine (T-DM1) for clinical use represented a turning point both in HER2-positive breast cancer treatment and antibody-drug conjugate (ADC) technology. T-DM1 has proved its value and effectiveness in advanced metastatic disease as well as in the adjuvant setting. However, its therapeutic potential extends beyond the treatment of breast cancer. Around 100 clinical trials have evaluated or are studying different aspects of T-DM1, such as its role in other HER2 malignancies, rational combinations with immunotherapy, or its function in brain metastasis. Conceptually, many lessons can be learned from this ADC. Understanding its mechanisms of action and the molecular basis underlying resistance to T-DM1 may be relevant to comprehend resistances raised to other ADCs and identify pitfalls that may be overcome.
MeSH term(s)	Ado-Trastuzumab Emtansine/pharmacology ; Ado-Trastuzumab Emtansine/therapeutic use ; Antineoplastic Agents, Immunological/pharmacology ; Antineoplastic Agents, Immunological/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Breast/pathology ; Breast/surgery ; Breast Neoplasms/immunology ; Breast Neoplasms/mortality ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; Chemotherapy, Adjuvant/methods ; Clinical Trials as Topic ; Drug Resistance, Neoplasm/drug effects ; Female ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Immune Checkpoint Inhibitors/therapeutic use ; Immunotoxins/pharmacology ; Immunotoxins/therapeutic use ; Mastectomy ; Neoadjuvant Therapy/methods ; Progression-Free Survival ; Receptor, ErbB-2/antagonists & inhibitors ; Receptor, ErbB-2/metabolism
Chemical Substances	Antineoplastic Agents, Immunological ; Immune Checkpoint Inhibitors ; Immunotoxins ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1) ; Ado-Trastuzumab Emtansine (SE2KH7T06F)
Language	English
Publishing date	2020-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2019.12.010
Database	MEDical Literature Analysis and Retrieval System OnLINE

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