Pancreatic cancer is one of the most difficult malignancies worldwide, with very low survival rates. The lack of specific symptoms and clinical features contributes to this, which leads to delayed diagnosis, with the majority of patients (a percentage of around 60-80%) being finally diagnosed at a locally advanced or metastatic stage, with a negative prognosis.

Risk factors include the aging of the planet’s population, obesity, diabetes, smoking and frequent alcohol consumption.

Today, advances in antitumor therapy have led to encouraging results in the management of oncological patients, with increased survival, improved quality of life and optimization of treatments, with the use of targeted agents and immunotherapy.

“What was true until recently and for many years, – depending on the stage of the disease – surgery, chemotherapy and radiotherapy, alone or in combination, were the treatment options of an oncologist. Chemotherapy, either with the combination of 5FU, Leucovorin, Oxaliplatin, Irinotecan (FOLFIRINOX), or with the combination of Abraxane – Gemcitabine, was the cornerstone of the treatment of patients with inoperable pancreatic cancer”, points out Nikolaos Kentepozidis, MD, MSc, PhD Pathologist Oncologist Director of the 4th Oncology Clinic Metropolitan General.

“In recent years, some genes have been found, the mutations of which lead to an increased probability of pancreatic adenocarcinoma compared to the average population. This category includes somatic mutations in the genes BRCA 1 and BRCA 2 (breast Ca and ovarian Ca), ATM (ataxia telangiectasia), STK11 (Peutz-Jeghers syndrome), MLH1 and MSH2, MSH6 (Lynch syndrome). The understanding of the pathophysiology of pancreatic adenocarcinoma, as well as the discovery of the above genes and the entry of immunotherapy into this malignancy, have offered additional options in the therapeutic management of patients with advanced disease”, continues the expert and adds:

“Immunotherapy uses specific parts of the patient’s own immune system to fight malignancies. The very encouraging results given by the use of immunotherapy in tumors such as lung cancer, bladder cancer and melanoma, led to the expansion to tumors with less immunogenicity, such as pancreatic cancer.

In fact, the understanding of the molecular mechanisms that govern the immune escape of tumors, but also the interaction of cancer cells with the cells of the immune system, has given impetus to the immunotherapy of pancreatic cancer, especially those patients who have a high expression of PD- L1 or have tumor microsatellite instability (MSI-h), which was also shown by the results of KEYNOTE-158 with pembrolizumab in non-colorectal cancer patients with MSI-h/MMR-d”.

“PARP inhibitors are a class of drugs that contribute to the process of responding to any cellular DNA damage, such as DNA damage repair, gene transcription, and cell death.

The cytostatic action of PARP inhibitors is exerted through two mechanisms, the inhibition of PARP catalytic activity and the trapping of PARP in DNA. This category includes olaparib, which is used in patients with ovarian cancer, breast cancer and prostate cancer who have BRCA 1 and BRCA 2 gene mutations.

Thus, through the POLO study, olaparib has been approved as oral monotherapy for the maintenance treatment of patients with BRCA 1 and BRCA 2 gene mutations who have not experienced disease progression after first-line treatment with a platinum combination.
NTRK1, NTRK2, NTRK3 genes play an important role in cell proliferation and cell differentiation. Mutations between NTRK genes result in the creation of fusion proteins, which are overexpressed and act uncontrollably resulting in the development of malignancy.

Anti-NTRK drugs were approved based on mutation and primary tumor. Thus, larotrectinib and entrectinib are drugs approved for pancreatic cancer patients with NTRK mutations, rearrangements, or amplification, and these patients can receive the oral treatment,” emphasizes Mr. Kentepozides.

“In conclusion” he concludes, “the most encouraging message is that in the era of personalized treatment, our treatment options have increased, even in a disease with not so good prognosis and survival, such as pancreatic cancer. Having, therefore, a molecular profile of the tumor and using the appropriate biomarkers, the goal of every oncologist should be to administer the appropriate drug (immunotherapy, targeted therapies) to the appropriate patient.”