Breast cancer relapse could be triggered by chemotherapy damage to non-cancerous cells

Standard chemotherapy drugs damage surrounding non-cancerous cells, which can then awaken dormant or dormant cancer cells and promote cancer growth.

This is one of the conclusions of a study that has just been published in the journal Plos Biology, led by Ramya Ganesan of Emory University, in the USA.. The finding is important for understanding cancer recurrence and may open the door to new approaches and approaches.

Advances in cancer treatment, including new generations of chemotherapy, have significantly reduced mortality from many types of cancer, including breast cancer.. However, up to 23% of breast cancer patients experience a relapse within the first five years.. Treatment aims to destroy all cancer cells, but some cells often enter a state of dormancy, in which they stop dividing and stop responding to chemotherapy agents.. Recurrence occurs when dormant cells reawaken and begin dividing again.

Some studies have indicated that chemotherapy itself may promote escape from torpor, but the mechanism of this effect has not been clear.. To explore that question, the authors of this study worked with a cell model and a mouse model of breast cancer.

Importantly, the cell model contained both cancer cells and noncancerous stromal cells, connective tissue cells found in the breast and other tissues.

Damage to stromal cells

To carry out the research, they administered the chemotherapy drug docetaxel at physiologically relevant concentrations and discovered that even at very low doses, stromal cells were damaged, while cancer cells were not, and that the treatment induced cell cycle re-entry. in cancer cells.

What drives this awakening

The authors showed that the driver of this awakening of dormant cells was the release of two key cell signaling molecules, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6) by the injured stromal cells, which acted on dormant cells to promote their growth, both in vitro and in vivo.

This finding provided potential anticancer targets, and the researchers were able to show that antibodies that neutralized G-CSF or IL-6, or a drug that blocked the mediator of those signals within cancer cells, inhibited awakening from dormancy due to to treatment with docetaxel.

These observations provide several important implications, according to the study's authors.. First, they highlight the importance of surrounding cells, not just the cancer cells themselves, in determining response to chemotherapy.. Furthermore, they provide a possible mechanistic basis for the observation that elevated serum levels of IL-6 are associated with early recurrence in breast cancer patients receiving chemotherapy, potentially strengthening the utility of that biomarker in treatment planning.. Third, they provide new targets for preventing recurrence.

Ramya Ganesan explains that her research reveals “a deleterious effect of cancer chemotherapy,” from the release of stromal IL-6 and G-CSF by taxane chemotherapy, which “awakened dormant breast cancer cells, a postulated mechanism for tumor relapse,” while highlighting that transient blockade of cytokine signaling during chemotherapy administration may prevent tumor recurrence.”

In his analysis of the work for Science Media Center (SMC) Spain Joan Albanell, head of the Department of Medical Oncology at the Hospital del Mar in Barcelona, highlights that the methodology is adequate “but limited to preclinical models so its translation to the clinic is determined”.

This study, according to Albanell, adds to the growing evidence that chemotherapy can damage non-tumor cells that are part of cancers and specifically demonstrates that it can reactivate the growth of dormant tumor cells.. Importantly, it describes mechanisms causing this tumor re-emergence in breast cancer that can be counteracted pharmacologically at an experimental level.. However, this expert points out that the translation of this research to the clinic “is still a question mark.”

For his part, Javier Cortés, director of the International Breast Cancer Center IBCC (Barcelona), founding partner of Medica Scientia innovation Research (MedSIR), a company dedicated to the development of clinical trials, and senior clinical researcher of the breast cancer research program of the Vall d'Hebron Oncology Institute has also pointed out to SMC Spain that we must take into account, first of all, that “cancer is a whole; there may be a negative interaction with one part, but a very positive one with another, the balance being absolute positive”. In that sense, he emphasizes that “there are studies that have compared giving or not giving taxanes [a type of chemotherapy] and the benefits in favor of giving them are very clear.”