Cell Cycle & Cancer Biomarkers Group - (CCCB)

Introduction

More info here: CCCB lab WEB PAGE

Cancer is one of the main causes of mortality and its complexity grows as different types of cancer can be further classified into different subtypes. To deepen the knowledge concerning the molecular mechanisms associated with cancer is essential for the development of new therapeutic strategies, with the final goal to reach the concept of "personalized medicine".

Alterations in cell cycle progression, high rates of cell proliferation and chromosomal instability are common features of multiple tumors. Numerous cell cycle regulators are overexpressed in tumors and very often this correlates with poor clinical prognosis. Nevertheless, proper identification of reliable biomarkers related to cell cycle, which not only correlate to prognosis but also provide a therapeutic value, is still lacking.

Classical chemotherapy, although effective in a percentage of cases, is associated with severe cytotoxic side effects. As an alternative, pharmaceutical companies are developing new inhibitors against specific molecular targets of high therapeutic value. Unfortunately, the newly designed drugs, although effective in certain types of tumors are not as efficient as initially thought. Therefore, to increase the knowledge about the molecular basis of certain tumors, as well as to identify mechanisms of sensitivity and resistance to newly developed drugs, is of great interest to the medical community and for upcoming cancer patients.

The main interest of the Cell Cycle & Cancer Biomarkers laboratory (CCCB) is to understand and define oncogenic mechanisms of cell cycle regulators with the ultimate goal to translate this knowledge to the clinic.

Current Research Projects

Deregulation of cell division is a common feature in multiple types of tumors. Tumor cells cancel the control mechanisms of the cell cycle, resulting in the accumulation of genetic aberrations. In recent decades, as an anticancer strategy effort, researchers and pharmaceutical companies have developed a collection of drugs to stop cell division, in order to kill tumoral cells, by inhibiting the main mitotic kinases such as the Cycle-Dependent Kinases (CDKs), the family of Aurora kinases and the family of Polo-like kinases (PLKs).

We pretend to use cell cycle regulators as biomarkers form cancer therapy, with the goal to find new therapeutic opportunities. Concomitantly, this will provide us the possibility to understand the mechanisms by which those cell cycle regulators modulate the oncogenic status of tumoral cells.

We address this by three different approaches:

1. Drug sensitivity screenings: Cell division genes are often overexpressed in tumors, and this commonly confers poor prognosis to the patients. We want to evaluate if the expression of certain mitotic genes can predict sensitivity to different pharmacologic drugs.

- In collaboration with the pharmaceutical company Lilly.

- Sponsored by the AECC (Spanish Association Against Cancer)

2. Cell Cycle Drugs Resistance Mechanisms: A recurring problem in therapies with kinase inhibitors is the appearance of drug resistance mechanisms and therefore the loss of efficacy over time. Given the recent emergence of a new generation of cell division cancer drugs, the need to identify new resistance mechanisms increased substantially.

- Sponsored by the AECC (Spanish Association Against Cancer)

3. Mitotic regulators: Oncogenes or tumor suppressors?: An interesting feature of cell division genes is that they are often overexpressed in cancer, and this confers poor prognosis to the patients. This is typically symbolized by the master mitotic regulator Plk1 (Polo-Like Kinase 1). Plk1 has been considered an oncogene during decades. Surprisingly, in recent years, solid data emerged indicating that Plk1 can also have a role as a tumor suppressor. The logical and immediate question that then arises is: When can Plk1 act as a tumor suppressor or as an oncogene?


de Cárcer Díez, Guillermo
Investigador Titular



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