Lysosomes and endoplasmic reticulum: targets for improved, selective anticancer therapy

Area of Science:

• Oncology
• Cell Biology
• Molecular Biology

Background:

• Conventional anticancer agents target proliferating cells, but tumor cells often develop resistance.
• Apoptosis signaling pathways are frequently impaired in cancer, limiting treatment efficacy.
• Lysosomes and the endoplasmic reticulum (ER) are emerging as promising targets due to their roles in apoptosis and potential resistance mechanisms.

Purpose of the Study:

• To explore the potential of targeting lysosomes and ER for inducing cancer cell death.
• To investigate if organelle damage responses can overcome therapy resistance in tumor cells.
• To evaluate the feasibility of manipulating ER stress for anticancer therapy.

Main Methods:

• Analysis of lysosomal cathepsin activity in tumor cells.
• Investigation of ER stress induction by anticancer drugs.
• Assessment of tumor cell sensitivity to organelle-targeting strategies.

Main Results:

• Tumor cell lysosomes exhibit elevated cathepsin levels, and their release can trigger apoptosis or necrosis.
• Tumor transformation increases sensitivity to cathepsin B-dependent apoptosis.
• Tumor cells often experience constitutive ER stress, which can be manipulated by certain anticancer drugs.

Conclusions:

• Organelle damage responses, particularly in lysosomes and ER, can be harnessed to induce tumor cell death.
• Targeting these organelles offers a strategy to overcome resistance to conventional DNA-damaging anticancer agents.
• Manipulating ER stress represents a viable therapeutic avenue for cancer treatment.