Controversies in clinical cancer dormancy

Abstract

Clinical cancer dormancy is defined as an unusually long time between removal of the primary tumor and subsequent relapse in a patient who has been clinically disease-free. The condition is frequently observed in certain carcinomas (e.g., breast cancer), B-cell lymphoma, and melanoma, with relapse occurring 5–25 y later. Clinical data suggest that a majority of breast cancer survivors have cancer cells for decades but can remain clinically cancer-free for their lifetime. Thus, there is a major effort to characterize the molecular mechanisms responsible for inducing tumor cell dormancy using experimental models or studying the early phases of cancer growth in humans. Many molecules and signaling pathways have been characterized and have led to concepts that dominate the field, such as the possible role of innate and adaptive immunity in immune surveillance and initiation and maintenance of dormancy. However, recent clinical data do not support many of these concepts. Several areas need further study to determine their relevance to clinical cancer dormancy. We suggest hypotheses that may contribute to elucidation of the mechanisms underlying the dormant state.

SMAD signaling and redox imbalance cooperate to induce prostate cancer cell dormancy

“…[1][2][3][4][5] In humans, the phenomenon of dormancy also accounts for metastatic recurrences appearing up to several decades after the cure of the primary cancer, as observed in breast and prostate cancers, some leukemia and melanoma. [6][7][8][9][10][11] These recurrences are also in agreement with the observation that dormant cells are more resistant to chemotherapy than the primitive cancer cells, which makes them very difficult to eradicate.…”

Inhibition of RON kinase potentiates anti-CTLA-4 immunotherapy to shrink breast tumors and prevent metastatic outgrowth

“…Many tumors have spawned micrometastases to other organs before the primary tumor is diagnosed. These micrometastases can then grow into overt metastatic disease at distant sites, 56 and adjuvant chemotherapy is intended to eliminate microscopically seeded cells. Distant recurrence rates for breast cancer are still between 20–30%, 57 indicating the need for better therapies to kill previously seeded micrometastases.…”

Oncogenes and the coagulation system – forces that modulate dormant and aggressive states in cancer

“…As mentioned earlier, several human tissues contain morphologically transformed but dormant cells, and such cells can also be found in the bone marrow of patients in remission after clinically effective anticancer treatment [105,[110][111][112]. Exit from such a quiescent state represents an important and potentially targetable event in the onset and progression of the malignant disease [110].…”