Neuroendocrine tumors (NETs) develop in the hormone-producing cells of the body’s neuroendocrine system. NETs can occur in various organs, and pancreatic neuroendocrine tumors (PNETs) are rare and often diagnosed at a later stage.

The treatment for PNETs typically involves surgery, and chemotherapy is used in advanced cases, but these treatment options are not fully effective. Therefore, there is a need for new treatment options for PNETs.

What are PNETs?

PNETs are rare malignant tumors that arise from the endocrine cells in the pancreas, a gland that plays a vital role in digestion and glucose metabolism.

PNETs are usually slow-growing, and the symptoms may not appear until the tumor has spread to other organs. The cause of PNETs is not fully understood, but certain genetic syndromes like multiple endocrine neoplasia type 1 (MEN1) and von Hippel-Lindau syndrome (VHL) are linked to an increased risk of developing PNETs.

The Role of Proteins in PNETs

Proteins are molecules made up of amino acids that play a critical role in the function of cells. In PNETs, certain proteins are over-expressed or mutated, which leads to uncontrolled cell growth and tumor formation.

One such protein is insulin-like growth factor-1 receptor (IGF-1R), which is known to play a role in cell proliferation, differentiation, and survival. The overexpression of IGF-1R has been observed in several types of cancer, including PNETs.

The Potential of Inhibiting IGF-1R in PNETs

Targeting IGF-1R has been a topic of interest in cancer research due to its role in cancer cell growth and survival.

Several studies have shown that inhibiting IGF-1R can lead to reduced cell proliferation, decreased tumor growth, and increased sensitivity to chemotherapy. There are several IGF-1R inhibitors in clinical trials for various types of cancer, including PNETs.

Clinical Trials with IGF-1R Inhibitors

A phase 2 randomized clinical trial studied the effects of the IGF-1R inhibitor, ganitumab, in patients with advanced PNETs.

The study involved 160 patients and showed an improvement in progression-free survival (PFS) in patients who received ganitumab with octreotide LAR compared to those who received only octreotide LAR. Ganitumab did not show any significant difference in overall survival (OS) compared to the control group.

Limitations and Side Effects of IGF-1R Inhibitors

While IGF-1R inhibitors show promise as a potential treatment for PNETs, there are several limitations and side effects associated with their use. One challenge is identifying the patients who are most likely to benefit from IGF-1R inhibition.

The efficacy of IGF-1R inhibition may be influenced by the tumor type, the stage of the tumor, and the presence of certain genetic mutations. In addition, IGF-1R inhibitors may cause side effects like hyperglycemia, hypoglycemia, and skin rash.

Conclusion and Future Directions

PNETs are a rare type of cancer with limited treatment options. The overexpression of proteins like IGF-1R plays a critical role in tumor growth, and targeting these proteins has shown promising results in clinical trials.

While IGF-1R inhibitors have demonstrated efficacy in improving PFS in patients with advanced PNETs, more research is needed to identify the patients who are most likely to benefit from this treatment. Additionally, combination therapy with other targeted agents or chemotherapy may also improve the efficacy of IGF-1R inhibitors in treating PNETs.