Pancreatic Ductal Adenocarcinoma (PDAC) Treatment Gains a Boost with New Gene Markers

Pancreatic ductal adenocarcinoma (PDAC) is a common neoplastic disease of the pancreas. PDAC is a highly aggressive and very lethal malignant tumor. Malignant PDAC is usually not diagnosed early and can lead to a high mortality rate. At the time of diagnosis, several patients have an unresectable, metastatic, locally advanced tumor. The inefficiency of conventional treatment options such as chemotherapy, surgery, and radiation makes it difficult for total recovery from PDAC. However, in recent times, immunotherapy has gained successful application in managing this highly lethal pancreatic tumor. The desire to find better treatment options for PDAC has dominated the literature for years. A team of scientists has successfully identified gene markers that could revolutionize PDAC treatment, potentially leading to more effective and precise management.

CT Image of Pancreatic Cancer.

New protein biomarker leads to a better outcome in PDAC patients

The use of Poly-ADP-ribose-polymerase inhibitors (PARPi) is common and recommended for the treatment of patients with PDAC. However, this treatment option applies to only a limited number of patients with PDAC. The lack of patients with pathogenic mutations of the homologous recombination gene limits the treatment approach of PARPi. These leave a high number of patients missing out on therapy.

In this groundbreaking study, the study scientists discovered the protein METTL16 may be a new potential biomarker for PARPi in PADC treatment. They found that patients with an increased expression of the METTL16 biomarker can benefit from this treatment option.

The biomarker is part of a group of genetic factors that regulates RNA methylation. Thus, the biomarker expresses not through protein-to-protein interaction but through RNA. The METTL16 biomarker suppresses DNA repair via an interaction with a key DNA repair nuclease.

PDAC cells with high METTL16 expression were more sensitive to PARPi in both cellular and mouse models, especially when combined with gemcitabine. The increased sensitivity is because METTL16 is highly expressed in a subset of PDAC and inhibits homologous recombination. These novel findings show that elevated METTL16 may also be a target for PARPi treatment.

Clinical significance

The highly lethal pancreatic cancer has been elusive to therapy for decades. There is a failure of conventional treatment methods to manage PDAC. This failure presents an increased mortality rate of the disease. Even with the development of an immunotherapeutic approach using PARPi, there are still genetic restrictions in a high number of patients. The current study proves clinically significant in showing a novel protein biomarker with increased sensitivity to immunotherapy. These findings could be beneficial in developing better treatment outcomes for PDAC.

Conclusion

The need for more effective methods of managing PDAC is pressing. With a high mortality rate globally and conventional therapy resistance, the deadly pancreatic tumor has been subject to many studies. The findings from this study allow for a newer approach with protein biomarkers and PARPi to give more precise treatment. The increased sensitivity of METTL16, in combination with gemcitabine, causes an increased patient’s sensitivity to PARPi.