Autophagy is a self-degradative process in response to stresses by which damaged macromolecules and organelles are targeted by autophagic vesicles to lysosomes and then eliminated. Autophagy has been described to play a role in physiological processes and a variety of human diseases, including cancer. Autophagy regulation is strictly interconnected with the aberrant setting of cancer cell metabolism as revealed by the fact that mTOR and AMPK pathways are both the master regulators of autophagy and the most critical sensors of the cellular energy status. The role of autophagy in regulating cancer cell death or survival remains highly controversial and it is likely reliant on the tumor type, the stage of neoplasia and the cellular context, as well as by metabolic context in which the cells lie. In this regards, many studies have shown that in established tumors, constitutive autophagy may have a protective role in cancer cells by removing damaged organelles or recycling misfolded macromolecules. However, it is also well established that cancer cells having uncontrolled autophagy can also undergo cell death, also called cell death-type II, likely due to excessive degradation of cellular constituents and organelles required for homeostasis of the cells. Hence, autophagy has been widely established as a tumor-suppressive mechanism, and cancer cells can escape from extensive autophagic cell death resulting in the enhancement of ROS production, genomic instability, and tumor progression.
In this regard, the possibility to modulate autophagy may represent a valid therapeutic approach to treat different types of cancers and a variety of clinical trials, using autophagy modulators, are currently employed. For instance, in tumors with enhanced autophagy, as a mechanism of survival and chemoresistance, the inhibition of autophagy can suppress the ability of tumor cells to survive under cellular metabolic stress making them more prone to initiate cell death mechanisms. In this sense, there are a variety of examples showing that autophagy inhibitors, as inhibitor of 3-methyl-adenine (3-MA) or chloroquine (CQ), when used in combination with anticancer drugs, may sensitize chemoresistant cells, thus inhibiting tumor survival. However, excessive autophagy induction upon cytotoxic drug treatments or using autophagy inducers, as mTOR inhibitors, may also lead to autophagic cell death.
On the other hand, recent progress in nanotechnology offers plenty of tools to fight cancer with innovative and efficient therapeutic agents by overcoming obstacles usually encountered with traditional drugs. Interestingly, nanomaterials have been explored as potent modulators of autophagy through multiple mechanisms, and have been exploited as therapeutic agents against cancer. For this reason, autophagy modulation with chemotherapy drugs, including nanoparticle-based strategies, would acquire clinical relevance in the near future, as a complementary therapy for the treatment of cancers.
This Research Topic of Frontiers in Pharmacology focuses on novel drugs and nanomaterials in cancer treatment based on autophagy modulation and the related molecular mechanisms underlying. We encourages basic and translational scientists working in a related field to submit high quality original articles, clinical trials, solicited and unsolicited review articles.
Autophagy is a self-degradative process in response to stresses by which damaged macromolecules and organelles are targeted by autophagic vesicles to lysosomes and then eliminated. Autophagy has been described to play a role in physiological processes and a variety of human diseases, including cancer. Autophagy regulation is strictly interconnected with the aberrant setting of cancer cell metabolism as revealed by the fact that mTOR and AMPK pathways are both the master regulators of autophagy and the most critical sensors of the cellular energy status. The role of autophagy in regulating cancer cell death or survival remains highly controversial and it is likely reliant on the tumor type, the stage of neoplasia and the cellular context, as well as by metabolic context in which the cells lie. In this regards, many studies have shown that in established tumors, constitutive autophagy may have a protective role in cancer cells by removing damaged organelles or recycling misfolded macromolecules. However, it is also well established that cancer cells having uncontrolled autophagy can also undergo cell death, also called cell death-type II, likely due to excessive degradation of cellular constituents and organelles required for homeostasis of the cells. Hence, autophagy has been widely established as a tumor-suppressive mechanism, and cancer cells can escape from extensive autophagic cell death resulting in the enhancement of ROS production, genomic instability, and tumor progression.
In this regard, the possibility to modulate autophagy may represent a valid therapeutic approach to treat different types of cancers and a variety of clinical trials, using autophagy modulators, are currently employed. For instance, in tumors with enhanced autophagy, as a mechanism of survival and chemoresistance, the inhibition of autophagy can suppress the ability of tumor cells to survive under cellular metabolic stress making them more prone to initiate cell death mechanisms. In this sense, there are a variety of examples showing that autophagy inhibitors, as inhibitor of 3-methyl-adenine (3-MA) or chloroquine (CQ), when used in combination with anticancer drugs, may sensitize chemoresistant cells, thus inhibiting tumor survival. However, excessive autophagy induction upon cytotoxic drug treatments or using autophagy inducers, as mTOR inhibitors, may also lead to autophagic cell death.
On the other hand, recent progress in nanotechnology offers plenty of tools to fight cancer with innovative and efficient therapeutic agents by overcoming obstacles usually encountered with traditional drugs. Interestingly, nanomaterials have been explored as potent modulators of autophagy through multiple mechanisms, and have been exploited as therapeutic agents against cancer. For this reason, autophagy modulation with chemotherapy drugs, including nanoparticle-based strategies, would acquire clinical relevance in the near future, as a complementary therapy for the treatment of cancers.
This Research Topic of Frontiers in Pharmacology focuses on novel drugs and nanomaterials in cancer treatment based on autophagy modulation and the related molecular mechanisms underlying. We encourages basic and translational scientists working in a related field to submit high quality original articles, clinical trials, solicited and unsolicited review articles.
