Pancreatic Disorders & Therapy
Open Access

Navigating Pancreatic Cancer: The Role of Autophagy in Therapeutic Approaches

Marteena Luther^{* *}Correspondence: Marteena Luther, Department of Hepatobiliary and Pancreas Surgery, Shree Guru Gobind Singh Tricentenary University, Haryana, India, Email:

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Description

Pancreatic cancer remains one of the most challenging malignancies to treat, with limited therapeutic options and a high mortality rate. Recent advancements in cancer research have illuminate on the role of autophagy, a cellular selfdegradation process, in the development and progression of pancreatic cancer. Understanding the therapeutic aspects and molecular targets of autophagy opens new avenues for innovative approaches to manage this deadly disease. Autophagy, derived from the Greek words "auto" (self) and "phagy" (eating), is a highly conserved cellular process responsible for degrading and recycling damaged or unnecessary cellular components. It plays a crucial role in maintaining cellular homeostasis and is implicated in various physiological and pathological conditions, including cancer. In pancreatic cancer, dysregulation of autophagy contributes to the survival and growth of cancer cells. Pancreatic tumors often exploit autophagy to cope with nutrient deprivation, oxidative stress, and other adverse conditions within the tumor microenvironment. Understanding the dual role of autophagy in cancer—either promoting cell survival or inducing cell death—provides a foundation for developing targeted therapeutic strategies.

Therapeutic aspects of autophagy in pancreatic cancer

Autophagy inhibition: Targeting autophagy with pharmacological inhibitors has emerged as a potential therapeutic strategy. Chloroquine and hydroxychloroquine, which inhibit the late stages of autophagy, have been investigated in preclinical and clinical studies for pancreatic cancer treatment. These drugs disrupt the autophagic flux, leading to the accumulation of damaged cellular components and eventual cell death.

Autophagy induction: Paradoxically, inducing autophagy may also be a viable therapeutic approach. Certain drugs, such as rapamycin and its analogs, stimulate autophagy and have shown compact in preclinical studies. Inducing autophagy may sensitize cancer cells to other forms of treatment, such as chemotherapy and radiation.

Dual-targeted therapies: Combining autophagy-targeted therapies with conventional anticancer treatments represents a synergistic approach. Dual-targeted therapies aim to exploit the vulnerabilities of cancer cells by inhibiting autophagy while concurrently delivering traditional treatments like chemotherapy. This combinatorial approach enhances treatment efficacy and minimizes the risk of resistance development.

Molecular targets of autophagy in pancreatic cancer

mTOR pathway: The mammalian Target Of Rapamycin (mTOR) pathway is a central regulator of autophagy. Inhibition of mTOR can induce autophagy and has been investigated as a therapeutic target in pancreatic cancer. mTOR inhibitors, such as rapamycin and everolimus, have been studied for their ability to modulate autophagy and inhibit cancer cell proliferation.

PI3K/Akt pathway: The phosphoinositide 3-kinase (PI3K)/Akt pathway is another critical regulator of autophagy. Dysregulation of this pathway is common in pancreatic cancer. Targeting PI3K/Akt signaling can influence autophagy and inhibit cancer progression. Dual inhibitors of PI3K and autophagy have shown promise in preclinical studies.

p53 and AMPK: The tumor suppressor protein p53 and the Adenosine Monophosphate-activated Protein Kinase (AMPK) are key regulators of autophagy. Modulating these pathways can impact autophagic activity and influence the fate of cancer cells. Strategies that activate p53 or AMPK may hold therapeutic potential in pancreatic cancer.

Conclusion

Autophagy plays a complex role in pancreatic cancer, influencing both tumor promotion and suppression. Harnessing the therapeutic aspects of autophagy and targeting specific molecular pathways offer favorable for managing pancreatic cancer. As research continues to unravel the intricate connections between autophagy and cancer biology, innovative and targeted therapeutic strategies may hold the key to improving outcomes for patients with this devastating disease.