Tumor cell lysosomal compartment

The tumor cell lysosomal compartment is an acidic organelle system primarily responsible for macromolecular degradation, nutrient sensing, and the regulation of autophagy (Kirkegaard & Jäättelä, 2009). In malignant cells, lysosomes are often enlarged and more fragile, characterized by an over-expression of proteolytic enzymes like cathepsins that facilitate invasion and metastasis (Piao & Amaravadi, 2016). Therapeutic strategies targeting this compartment often aim to induce lysosomal membrane permeabilization (LMP), which releases these digestive enzymes into the cytoplasm to trigger apoptosis or necrosis (Boya & Kroemer, 2008). Additionally, lysosomotropic agents such as hydroxychloroquine are used to inhibit autophagy, thereby sensitizing tumor cells to chemotherapy and metabolic stress (Amaravadi et al., 2011). The lysosome also plays a critical role in drug resistance through the sequestration of hydrophobic weak base drugs, preventing them from reaching their intended intracellular targets (Zhitomirsky & Assaraf, 2016). Consequently, the lysosomal compartment represents a multifaceted target for overcoming chemoresistance and inducing selective cytotoxicity in cancer cells.

Other names

LysosomeLysosomal compartmentIntracellular organellesAcidic vesiclesCancer cell lysosome

Drugs targeting the lysosomal compartment typically act by increasing lysosomal pH, inhibiting autophagy, or inducing lysosomal membrane permeabilization (LMP) to trigger programmed cell death. Some agents are sequestered within the acidic environment, while others inhibit specific lysosomal enzymes (e.g., cathepsins) or transporters (e.g., V-ATPase) to disrupt cellular homeostasis and metabolic adaptation in tumor cells.