Translational Oncology

Research interests

The ultimate goal of our team is to attack tumors globally, not only targeting tumor cells but also their plasticity ability and controlling their interactions within the tumor niche, which are key players in the development of resistances in cancer.

Identification of new therapeutic vulnerabilities and development of combined therapies in breast and ovarian cancer: new therapies screening (PI. Alberto Ocaña)

From genetic studies, we identify alterations as overexpression of some genes that indicate a worse prognosis and that can be treated with new compounds as specific and selective inhibitors.

On the other hand, based on therapies already used in breast and ovarian cancer, we try to establish a possible synergistic relationship with new compounds that may be beneficial in clinical practice.

Our group has worked extensively in the evaluation of protein kinase inhibitors in breast cancer, mainly in triple negative tumors, and ovarian cancer identifying active drugs with great potential for clinical development.

2. Resistance to anticancer drugs (PI. Eva M. Galán Moya and Alberto Ocaña)

Frequently, tumors are or end up being refractory to chemotherapy and radiotherapy treatments, which makes them more invasive and more susceptible to have a worse prognosis.

Using a range of cells lines displaying different intrinsic sensibility and cell models with acquired resistance to drugs currently used in the clinic, established through a pulsed strategy, our group carries out proliferation and survival studies with new drugs to find mechanisms that reverse or overcome the resistance of these cells.

Proteolysis targeting chimeric (PROTAC) are novel compounds that promote protein degradation by binding to a ubiquitin ligase. In this research line, we also explore the antitumoral activity of novel PROTACs in resistant tumors.

3. Cancer cell plasticity and tumor microenvironment (PI. Eva M. Galán Moya).

For the past four decades, cancer research has been governed by a reductionist view of the disease. Most research has focused on studying tumor cells, ignoring the other components of the tumor. However, tumors behave like dynamic structures that require interaction with the surrounding environment, called the “tumor microenvironment” (TM), in order to grow. This microenvironment seems to play a key role in the behavior of tumors and, through the activation of certain signaling pathways, could be responsible for their aggressiveness and response to treatments. In addition, not all cancer cells are alike. Conversely, tumors display a high heterogeneity and usually comprise a population with higher plasticity and stemness properties known as cancer initiating cells (CIC), which usually are refractory to anti-cancer strategies. CIC constantly communicate with TM, and this communication might be responsible, at least in part, of the stemness potential of these cells and its intrinsic resistance.

Our team, using fresh samples of tumor and peritumoral tissue from patients with ovarian and breast cancer, has designed models for the study of the TM ex vivo. These models are being used not only to study the interactions between the different players, but also to test antitumor compound in a more physiological context, what is of interest for the design of combined therapies aiming tumor cell within its tumor niche in a global manner.

100% 100%

Funding

Título: Identificación y validación de nuevas dianas terapéuticas en cáncer de mama triple negativo mediante el uso de un modelo de microambiente tumoral mamario ex vivo. SBPLY/19/180501/000173.

Entidad financiadora: Junta de Comunidades de Castilla-La Mancha.

Tipo de proyecto: coordinado

Coordinador e Investigador Principal, IP1: EM. Galán Moya

IP2: Alberto Ocaña

Fecha inicio: 01/01/2020; fecha fin: 10/03/2023

Cuantía: 116.712 €.

Título: Targeting triple-negative and HER2-positive breast cancer with BET inhibitors and PROTACs. PI19/00808.

Entidad financiadora: Instituto de Salud Carlos III.

Investigador principal: Alberto Ocaña.

Fecha inicio 01/01/2020; fecha fin 31/12/2022.

Cuantía: 117.370 €.

Título: Estudio de la influencia del nicho adiposo en la iniciación, progresión y resistencia a fármacos en cáncer. DIPUAB17GALANMOYA

Entidad financiadora: Diputación de Albacete.

Investigador Principal: EM. Galan Moya.

Fecha inicio: 01/01/2017; fecha fin: 31/12/2017

Cuantía: 8.000 €.

Título: Identificación de vulnerabilidades en cáncer de mama triple negativo: análisis de la heterogeneidad clonal de subpoblaciones tumorales. PI16/01121.

Entidad financiadora: Instituto de Salud Carlos III.

Investigador principal: Alberto Ocaña.

Fecha inicio 01/01/2017; fecha fin 31/12/2019.

Cuantía: 142.285 €.

100% 100%

Publications

In silico transcriptomic mapping of integrins and immune activation in Basal-like and HER2+ breast cancer.

Rojas K, Baliu-Piqué M, Manzano A, Saiz-Ladera C, García-Barberán V, Cimas FJ, Pérez-Segura P, Pandiella A, Győrffy B, Ocana A.

Cell Oncol (Dordr). 2021 Jan 19. doi: 10.1007/s13402-020-00583-9. PMID: 33469836

Checkpoint Kinase 1 Pharmacological Inhibition Synergizes with DNA-Damaging Agents and Overcomes Platinum Resistance in Basal-Like Breast Cancer.

Nieto-Jimenez C, Alcaraz-Sanabria A, Martinez-Canales S, Corrales-Sanchez V, Montero JC, Burgos M, Nuncia-Cantarero M, Pandiella A, Galan-Moya EM*, Ocaña A*.

Int J Mol Sci. 2020 Nov 27;21(23):9034. doi:10.3390/ijms21239034.

PMID: 33261142

Controlled Delivery of BET-PROTACs: In Vitro Evaluation of MZ1-Loaded Polymeric Antibody Conjugated Nanoparticles in Breast Cancer.

Cimas FJ, Niza E, Juan A, Noblejas-López MDM, Bravo I, Lara-Sanchez A, Alonso-Moreno C, Ocaña A.

Pharmaceutics. 2020 Oct 19;12(10):986. doi: 10.3390/pharmaceutics12100986.

PMID: 33086530

Genomic Mapping Identifies Mutations in RYR2 and AHNAK as Associated with Favorable Outcome in Basal-Like Breast Tumors Expressing PD1/PD-L1.

Cimas FJ, Manzano A, Baliu-Piqué M, García-Gil E, Pérez-Segura P, Nagy Á, Pandiella A, Győrffy B, Ocana A.

Cancers (Basel). 2020 Aug 11;12(8):2243. doi: 10.3390/cancers12082243.

PMID: 32796628

Inhibition of the mitotic kinase PLK1 overcomes therapeutic resistance to BET inhibitors in triple negative breast cancer.

Nieto-Jimenez C, Galan-Moya EM*, Corrales-Sanchez V, Noblejas-Lopez MDM, Burgos M, Domingo B, Montero JC, Gomez-Juarez M, Picazo-Martinez MG, Esparis-Ogando A, Pandiella A, Ocaña A*.

Cancer Lett. 2020 Oct 28;491:50-59. doi: 10.1016/j.canlet.2020.06.020. PMID: 32735909

Topical Applications of Thiosulfinate-Enriched Allium sativum Extract Accelerates Acute Cutaneous Wound Healing in Murine Model.

Santiago JL, Galan-Moya EM, Muñoz-Rodriguez JR, de la Cruz-Morcillo MA, Redondo-Calvo FJ, Gracia-Fernandez I, Elias PM, Perez-Ortiz JM, Man MQ.

Chin J Integr Med. 2020 Nov;26(11):812-818. doi: 10.1007/s11655-020-3086-7. PMID: 32418180

Cost Effective Use of a Thiosulfinate-Enriched Allium sativum Extract in Combination with Chemotherapy in Colon Cancer.

Perez-Ortiz JM, Galan-Moya EM, de la Cruz-Morcillo MA, Rodriguez JF, Gracia I, Garcia MT, Redondo-Calvo FJ.

Int J Mol Sci. 2020 Apr 16;21(8):2766. doi: 10.3390/ijms21082766.

PMID: 32316312

Identification of a stemness-related gene panel associated with BET inhibition in triple negative breast cancer.

Serrano-Oviedo L, Nuncia-Cantarero M, Morcillo-Garcia S, Nieto-Jimenez C, Burgos M, Corrales-Sanchez V, Perez-Peña J, Győrffy B, Ocaña A, Galán-Moya EM.

Cell Oncol (Dordr). 2020 Jun;43(3):431-444. doi: 10.1007/s13402-020-00497-6. PMID: 32166583

Pharmacological screening and transcriptomic functional analyses identify asynergistic interaction between dasatinib and olaparib in triple-negative breast cancer.

Corrales-Sánchez V, Noblejas-López MDM, Nieto-Jiménez C, Pérez-Peña J, Montero JC, Burgos M, Galán-Moya EM, Pandiella A, Ocaña A.

J Cell Mol Med. 2020 Mar;24(5):3117-3127. doi: 10.1111/jcmm.14980.

PMID: 32032474

Genomic Signatures of Immune Activation Predict Outcome in Advanced Stages of Ovarian Cancer and Basal-Like Breast Tumors.

Alcaraz-Sanabria A, Baliu-Piqué M, Saiz-Ladera C, Rojas K, Manzano A, Marquina G, Casado A, Cimas FJ, Pérez-Segura P, Pandiella A, Gyorffy B, Ocana A.Front Oncol. 2020 Jan 10;9:1486. doi: 10.3389/fonc.2019.01486. eCollection 2019.PMID: 31998644

Expression of MHC class I, HLA-A and HLA-B identifies immune-activated breast tumors with favorable outcome.

Noblejas-López MDM, Nieto-Jiménez C, Morcillo García S, Pérez-Peña J, Nuncia-Cantarero M, Andrés-Pretel F, Galán-Moya EM, Amir E, Pandiella A, Győrffy B, Ocana A.

Oncoimmunology. 2019 Jul 3;8(10):e1629780. doi: 10.1080/2162402X.2019.1629780. PMID: 31646075

Activity of BET-proteolysis targeting chimeric (PROTAC) compounds in triple negative breast cancer.

Noblejas-López MDM, Nieto-Jimenez C, Burgos M, Gómez-Juárez M, Montero JC, Esparís-Ogando A, Pandiella A, Galán-Moya EM*, Ocaña A*.

J Exp Clin Cancer Res. 2019 Aug 30;38(1):383. doi: 10.1186/s13046-019-1387-5.

PMID: 31470872

Genetic mutational status of genes regulating epigenetics: Role of the histone methyltransferase KMT2D in triple negative breast tumors.

Morcillo-Garcia S, Noblejas-Lopez MDM, Nieto-Jimenez C, Perez-Peña J, Nuncia-Cantarero M, Győrffy B, Amir E, Pandiella A, Galan-Moya EM, Ocana A.

PLoS One. 2019 Apr 16;14(4):e0209134. doi: 10.1371/journal.pone.0209134. PMID: 30990809

Mapping Bromodomains in breast cancer and association with clinical outcome.

Pérez-Pena J, Páez R, Nieto-Jiménez C, Sánchez VC, Galan-Moya EM, Pandiella A, Győrffy B, Ocana A.

Sci Rep. 2019 Apr 5;9(1):5734. doi: 10.1038/s41598-019-41934-3.

PMID: 30952871

Evaluation of transcriptionally regulated genes identifies NCOR1 in hormone receptor negative breast tumors and lung adenocarcinomas as a potential tumor suppressor gene.

Noblejas-López MDM, Morcillo-García S, Nieto-Jiménez C, Nuncia-Cantarero M, Győrffy B, Galan-Moya EM*, Pandiella A, Ocaña A*.

PLoS One. 2018 Nov 28;13(11):e0207776. doi: 10.1371/journal.pone.0207776. PMID: 30485330

Functional transcriptomic annotation and protein-protein interaction analysis identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer.

Martínez-Canales S, López de Rodas M, Nuncia-Cantarero M, Páez R, Amir E, Győrffy B, Pandiella A, Galán-Moya EM*, Ocaña A*.

Cancer Med. 2018 May;7(5):1896-1907. doi: 10.1002/cam4.1406. PMID: 29575713

Functional transcriptomic annotation and protein-protein interaction network analysis identify NEK2, BIRC5, and TOP2A as potential targets in obese patients with luminal A breast cancer.

Nuncia-Cantarero M, Martinez-Canales S, Andrés-Pretel F, Santpere G, Ocaña A, Galan-Moya EM.

Breast Cancer Res Treat. 2018 Apr;168(3):613-623. doi: 10.1007/s10549-017-4652-3.

PMID: 29330624

Synthetic Lethality Interaction Between Aurora Kinases and CHEK1 Inhibitors in Ovarian Cancer.

Alcaraz-Sanabria A, Nieto-Jiménez C, Corrales-Sánchez V, Serrano-Oviedo L, Andrés-Pretel F, Montero JC, Burgos M, Llopis J, Galán-Moya EM, Pandiella A, Ocaña A.

Mol Cancer Ther. 2017 Nov;16(11):2552-2562. doi: 10.1158/1535-7163.MCT-17-0223.

PMID: 28847989

Transcriptomic immunologic signature associated with favorable clinical outcome in basal-like breast tumors.

Martínez-Canales S, Cifuentes F, López De Rodas Gregorio M, Serrano-Oviedo L, Galán-Moya EM, Amir E, Pandiella A, Győrffy B, Ocaña A.

PLoS One. 2017 May 4;12(5):e0175128. doi: 10.1371/journal.pone.0175128. PMID: 28472085

Targeting basal-like breast tumors with bromodomain and extraterminal domain (BET) and polo-like kinase inhibitors.

Nieto-Jiménez C, Alcaraz-Sanabria A, Pérez-Peña J, Corrales-Sánchez V, Serrano-Heras G, Galán-Moya EM, Serrano-Oviedo L, Montero JC, Burgos M, Llopis J, Pandiella A, Ocaña A.

Oncotarget. 2017 Mar 21;8(12):19478-19490. doi: 10.18632/oncotarget.14465.

PMID: 28061448