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SCIENTIFIC PROGRAMS

This include membrane transporters, phase I enzymes and antiapoptotic fac-
tors. Together with changes in expression, the onset of genetic variants cha-

racteristic of the patient or arising in the tumor during the carcinogenic process

can affect the function of these proteins and result in a lack of response to
chemotherapy.

2. Gastrointestinal and pancreatic oncology

Gastrointestinal and pancreatic cancer is responsible for most cancer-related
deaths. Reducing the number of deaths requires early detection. This is the ra-

tional basis for implementing population colorectal cancer screening programs,
currently in the phase of extension and evaluation. It is important to establish

which of the different existing strategies is the most effective and efficient for

medium-risk population screening, as well as which groups have an increased
risk of developing this tumor. Furthermore, the development and evaluation of

new non-invasive biomarkers that allow increasing participation in screening

and monitoring programs, increasing the diagnostic performance of strategies
currently used, and reducing potential complications resulting from said strate-

gies is fundamental. Finally, it is important to identify populations of individuals

with genetic or genomic characteristics that increase their susceptibility to de-
veloping these neoplasias.

3. Hepatic oncology

Liver cancer is a neoplasia that has experienced a rise in incidence in recent

years. The possibility of diagnosis in early stages of the disease and the availa-

bility of treatments that are proven effective for all stages of the disease have
brought about a great deal of research activity to improve knowledge about

molecular mechanisms determining their development and the most suitable

diagnosis and treatment strategy.

CIBEREHD groups lead the research in genetic signatures both for the de-
velopment of cancer in cirrhosis and for the progression and prognosis after

treatment. The groups are designing and running international clinical trials

for new drugs in phase 1-2, and in phase 3 both in first line and in second line
after conventional therapy has failed. Unfortunately, results up until now have

been negative. This may be because knowledge about the anomalies determi-
ning tumor progression is limited, and because the prognostic assessment and

design of trials for these patients must be innovated. In addition to intervention

studies, the usefulness of response markers is evaluated based on functional
imaging techniques and biological peripheral blood determinations.

4. Experimental hepatology and gene therapy

This field studies the mechanisms involved in the progression from chronic liver
damage to cirrhosis and hepatocarcinoma (HCC): disease markers and thera- 13
20
peutic relevance of hepatoprotective cytokines and growth factors. Methods T
based on cell therapy and gene therapy are also developed for the treatment of R
PO
cirrhosis of the liver and of primary and metastatic liver tumors. Immune mo- E
L R
dulation is being investigated for possible liver cancer immunotherapy and graft A
tolerance in liver transplant.
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