Abstract
Metastasis and relapse account for the great majority of cancer-related deaths. Most metastatic lesions are micro metastases that have the capacity to remain in a non-dividing state called “dormancy” for months or even years. Commonly used anticancer drugs generally target actively dividing cancer cells. Therefore, cancer cells that remain in a dormant state evade conventional therapies and contribute to cancer recurrence. Cellular and molecular mechanisms of cancer dormancy are not fully understood. Recent studies indicate that a major cellular stress response mechanism, autophagy, plays an important role in the adaptation, survival and reactivation of dormant cells. In this review article, we will summarize accumulating knowledge about cellular and molecular mechanisms of cancer dormancy, and discuss the role and importance of autophagy in this context.
Highlights
Cancer is the cause of death for millions of people every year, it’s one of the most devastating disease
Drug resistance and cancer dormancy are the two important causes of incurable metastatic disease that results in the loss of millions of lives from cancer-related deaths every year
Autophagy emerges as an integral part of the dormancy phenomenon
Summary
Cancer is the cause of death for millions of people every year, it’s one of the most devastating disease. Several independent studies using cancer cellsderived from a wide variety cancer types, including breast, ovary, gastrointestinal tract, pancreas and bone cancers and their respective mice tumor or xenograft models showed that, autophagy is highly active in dormant cancer cells [125, 148, 180, 198,199,200] Some of these observations were even supported by the analysis of patient-derived tissue samples [201], yet molecular details of how and why autophagy contributes to the dormant phenotype are not well known. Studies using different experimental set-ups, different cancer cell types and models revealed that, malignant cells entering a nonproliferative, dormancy-like but reversible cycle arrest state showed increased autophagic activity (Table 3) [148, 180, 199] In this context, dormant cancer cells were more sensitive to autophagy inhibition compared to their proliferating counterparts and inhibition of autophagy was lethal in most cases. Inhibition of DIRAS3-induced autophagy by chloroquine (a lysosomal autophagy inhibitor) reduced tumor growth, further underscoring the importance of autophagic activity to DIRAS3-related dormancy [202]
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