**3. Molecular biology and genetics**

treatments are no feasible to perform. To date, surgical resection is still the only potential curative treatment for the adenocarcinoma of the pancreas; however, only 15–20% of all the newly diagnosed patients will be candidates for curative pancreatectomy as an upfront

A complete radiological evaluation defines three subtypes of patients: metastatic and/or unresectable patients, resectable patients, and borderline resectable patients. This last group includes patients with vascular tumor compromise that could become resectable after an ade-

The prognosis of the pancreatic cancer is poor, even in those patients with resectable disease who underwent oncological surgery and adjuvant treatments if they were recommended, but also for those patients with borderline resectable disease who achieved oncological resection after neoadjuvant treatment that may include chemotherapy, radiotherapy, or a combination of both. Despite an optimal treatment, many of the resected patients will relapse within the 24 months after completing adjuvant treatment or after surgery. The 5-year survival following pancreaticoduodenectomy is only 25–30% for node-negative and 10% for node-positive tumors. The need to improve these results has led us to the development of new treatment

As mentioned earlier, pancreatic adenocarcinoma is one of the malignancies with worse prognosis among all solid tumors, with a small number of patients who will achieve cure after an optimal treatment, only if they have access to a good quality of cancer therapies based on specialized oncological surgeons who usually perform pancreas cancer surgery. In the United States, pancreatic cancer is the second most common malignant tumor of the gastrointestinal tract and the fourth malignancy related to cancer death in adults [1], with an estimated incidence of 48,960 new cases by 2015 and 40,560 deaths during the same year. Reported incidence and mortality are slightly higher in men than in women [2]. According to the reports of "Surveillance, Epidemiology and End Results Program" (SEER), the incidence of pancreatic adenocarcinoma is greater in males than in females (male-to-female ratio 1.3:1) and in Afro American population than in white population (14.8 per 100,000 in Afro American males compared with 8.8 per 100,000 in the general population) [3]. Worldwide, pancreatic cancer is the eighth leading cause of death related to cancer in men (138,100 deaths per year) and the ninth cause of death related to cancer among female population

In some developing Latin American countries, for reasons associated with industrialization and with the increasing life expectancy, pancreatic cancer and biliary tract malignancies are becoming more frequent diseases in adult population regardless of the educational and socioeconomical level. As an example, in Chile, one of the most developed countries in South America, with an estimated population of almost 17 million inhabitants, the reported annual

treatment.

180 Advances in Pancreatic Cancer

(per year) [4].

quate neoadjuvant treatment.

strategies that will be discussed ahead in this chapter.

**2. Epidemiology of the adenocarcinoma of the pancreas**

Several attempts looking for driver mutations and for trying to find target therapies to control pancreatic cancer spread have been made. Unfortunately, despite all the efforts, researchers have not conducted positive results in the clinical field, or at least their impact has not been relevant. Driver mutations such as KRAS, CDKN2A, TP53, and SMAD 4 have been involved in pancreatic cancer tumorigenesis [6], but without any impact on patients' selection of treatment yet. In other side, current immunotherapies that have achieved a great impact in the treatment of malignancies such as melanoma, lung cancer, bladder cancer, and others were not able to show benefit when tested in pancreatic cancer patients [7].

It is estimated that only 4–16% of pancreatic adenocarcinoma has a family history of this disease [8], while the rest of the cases may be considered as sporadic. To have a first-degree relative with an apparently sporadic pancreatic cancer has a moderate effect on the risk to develop this disease (odds ratio (OR), 1.76; 95% confidence interval (CI), 1.19–2.61) [9]. Selective mutations that have a recognized role in ovarian and breast cancer such as BRCA2 and, in a lesser degree, BRCA1 have been associated with familial pancreas cancer [10]. As previously mentioned, there are other selected genes that may have been associated with pancreatic cancer, for example, PALB2 [11], CDKN2A [12], and SMAD4 [13]. There are also genetic syndromes linked to pancreas cancer (e.g., hereditary pancreatitis, HNPCC, familial breast cancer with BRCA2 mutations, p16 mutations, Peutz-Jeghers syndrome, ataxia telangiectasia) [14]. Routine genetic testing for patients with newly diagnosed pancreatic cancer is controversial but it could give some clinical benefit by reducing the risk of associated cancers and by identifying family members of the index case who might benefit from screening for the cancer-predisposing mutation. Nevertheless, this is not considered a standard practice by current guidelines [15].
