These unique cell types can also trigger their own dormancy, allowing them to evade certain therapies.
- world day “Metastasis is a completely different reality because you know that now you are not going to be cured, your life and your survival depend on the new treatments that come out”
- Study Breast cancer spreads more while patients sleep
The triple negative breast cancer represents between a 10-15% of all breast tumors, among which are those positive for estrogen receptors, progesterone receptors and those that overexpress HER2.
Is considered more aggressive than the rest because it evolves quickly with greater chances of spread to diagnosis and increased risk of recurrence post-treatment against other types of breast cancer. In addition, currently, its therapeutic arsenal is more limited.
This scenario has awakened maximum interest of basic and clinical oncology that, in recent years, has offered interesting positive effects derived, for the most part, from the greater knowledge of the mechanisms of origin and tumor activity of the triple negative.
A new advance is achieved by scientists from the Tisch Cancer Institute of Mount Sina Hospital, in New York (United States)since they have just discover a mechanism for which certain breast cancer cells regulate their own metastasesThey drive spread from the original tumor site and determine routes to invade distant organs such as the lungs.
For the first time, this team has identified, and published in the latest Cell reports, a type of cancer cell in triple-negative breast tumors, which is very efficient at invading and colonizing distant organsbut which slows its growth after colonization, according to Jose Javier Bravo Corderoof Department of Hematology and Medical Oncology of the aforementioned center. “These cells have a hallmark of slow production of a protein called srGAP1which is generally attributed to tumor growth,” he says.
Tests in animal models have also shown that these unique cells trigger a phenomenon that keeps them in latency in distant organs such as the lungs, an important finding, Bravo believes, because “cancer cells have to survive efficiently in distant sites. Staying in this ‘sleeping’ existence allows them to avoid therapies focused on the rapid normal growth of cancer cells. Cells that are overlooked could become metastatic later”.
Marta Gonzalez Rodriguez, medical oncologist of the Breast Unit of the MD Anderson Cancer Center Madrid (Spain)points out to this newspaper: “Of course, the findings of the investigation carried out by the companions of Mount Sina are very interesting and open the door to the possible knowledge of metastatic tropism by one tissue or another, and probably in the future to find ‘targets’ to evade tumor cell invasion or metastases“.
The findings of this investigation, in which teams from New York State Universities at Stony Brook, Illinois in Chicago; California at Berkeley and the Janelia Research Campus of the Howard Hughes Medical Institute, highlight the importance of consider the phenotypic changes that might occur when cancer cells are treated with therapeutic strategies directed at proliferating cells, such as chemotherapy.
The director of the work indicates that “although these treatment regimens are directed at dividing cells, they may also be selecting more invasive tumor cells. Our studies suggest that they may be necessary more selective therapeutic strategies that combine treatments against dividing cells and invasive dormant cells to prevent metastatic disease.
Along these same lines, the MD Anderson Madrid oncologist considers that “the fact that there are quiescent cells or in the latent phase on which chemotherapy may not be as effective, and in many cases the response rate should be improved with treatment combinationsmaking use of immunotherapy, anti-angiogenic drugs or tyrosine kinase inhibitors, among others”.
To collect all the data, high resolution ‘in vivo’ images were used to visualize the extravasation or process by which tumor cells leave blood vessels to go to a target tissue; in this particular case, the lung. this phenomenon observed in real timerevealing in unprecedented detail the early stages of tumor extravasation.
Bravo Cordero goes on to point out that microscopy studies also revealed that after these ‘sleeping’ tumor cells invade the lungs they enter a dormant state by secreting the protein TGF2.
The studies also showed that interfering with this protein can block the invasion of tumor cells in the lungs, opening new pathways for the development of specific therapeutic strategies.
Ace, Gonzalez Rodriguez wonders: “Who knows if in the future we may disable proteins like srGAP1 or TGFb2 to prevent proliferation or invasion?” And the current response takes into account that the latter is the center of various studies in early phases, “some of whose results are promising, as is the case of bintrafuspalpha, a bifunctional fusion protein targeting TGFb and PDL1″, concludes the oncologist.