Descripción de la oferta
Immunomodulatory effects of ABTL0812, an autophagy-activating antitumor compound in clinical phase 2. Identification of new autophagy-based immunotherapeutic antitumor compounds.
Our laboratory is located at the Vall d’Hebron Hospital Research Institute (VHIR) Barcelona. We interested in dissecting new cellular signaling pathways that control cancer cell proliferation and differentiation. We aim to improve current anticancer treatments, combining molecular targeted therapy with other anticancer treatments, including chemotherapy and immunotherapy. We collaborate with Biopharma companies to help in the preclinical development of the anticancer drugs. Crucial for this project, we have played a fundamental role in the preclinical and clinical development of the new anticancer drug ABTL0812, which is currently in clinical trials 2b for endometrial, lung and pancreatic cancers. ABTL0812 induces autophagy-mediated cancer cell death by activating ER stress specifically cancer cells. In this project we will investigate the immunomodulatory properties of ABTL0812, and whether it potentiates the efficacy of immunotherapy (immune checkpoint inhibitors) in pancreatic cancer. We will also explore the anticancer activity and immunomodulatory properties of new pro-autophagy compounds.
Relevant publications from the group related to the project:
1. Yoldi et al. ABTL0812 potentiates standard chemotherapies and shows immune modulatory properties in preclinical models of pancreatic cancer. Submitted
2. Espinosa-Gil et al. ERK5/TP53INP2, a new signaling pathway that sensitizes cancer cells to death-receptor agonists and NK cells. Submitted
3. Muñoz-Guardiola et al. 2021. The anticancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells. Autophagy 17:1349-66.
4. Erazo et al. 2016. The New Antitumor Drug ABTL0812 Inhibits the Akt/mTORC1 Axis by Upregulating Tribbles-3 Pseudokinase. Clinical Cancer Research 22:2508-19.
5. Vidal et al. 2021. A first-in-human phase I/Ib dose-escalation clinical trial of the autophagy inducer ABTL0812 in patients with advanced solid tumours. European Journal of Cancer 146:87-94.
6. López-Plana A et al. 2020. The novel proautophagy anticancer drug ABTL0812 potentiates chemotherapy in adenocarcinoma and squamous nonsmall cell lung cancer. International Journal of Cancer 147:1163-1179
7. Polonio-Alcala et al. 2022. ABTL0812 enhances antitumor effect of paclitaxel and reverts chemoresistance in triple-negative breast cancer models. Cancer Communications 6:567-571.
8. Paris-Coderch et al. 2020. The antitumour drug ABTL0812 impairs neuroblastoma growth through endoplasmic reticulum stress-mediated autophagy and apoptosis. Cell Death and Disease 11:773.
9. Felip et al. 2019. Therapeutic potential of the new TRIB3-mediated cell autophagy anticancer drug ABTL0812 in endometrial cancer. Gynecologic Oncology. 153:425-435
Candidates should have a PhD in a relevant discipline (related to Biosciences).
A strong background and experience in Immunology is fundamental. Proven experience in working with animal models (mice) is also fundamental. Experience in cancer cell biology, cell cultures and flow cytometry is desirable.
The ideal candidate should be highly motivated with a strong interest in understanding and pursuing scientific questions. They should be able to work independently while interacting with other lab members.