La Dra. Matilde Lleonart publica un artículo sobre la resistencia a las terapias de algunos tumores

The group of Biomedical Research in Cancer Stem Cells of Vall d’Hebron Institute of Research (VHIR), led by Dr. Matilde Lleonart, has recently published an article in Cancer Treatment Reviews about the role of cancer stem cells in the resistance to the disease treatments.

Cancer stem cells are the origin of the most aggressive tumours. Cancer stem cells represent a percentage between 1% and 5% of the tumour mass, so it is not possible to detect them even on a microscopic scale. Contrary to differentiated tumour cells, cancer stem cells are located in a niche, isolated from the rest of the tumour and do not divide as fast as the rest of tumour cells. For this reason, the effects of radiotherapy and chemotherapy reach them, what makes them more resistant to treatment. All these characteristics make difficult to kill these cells during the treatment of the tumour, at least with the therapeutic tools used generally nowadays.

Another difficulty is that a differentiated cell –one which has already become a cell of a specific tissue- can become a cancer stem cell by a variety of cellular mechanisms. Dr. Lleonart explains that “this dynamism or tumour plasticity should be taken into account when planning the treatment of a tumour and apply a specific therapy for cancer stem cells combined with a conventional treatment of radiotherapy and chemotherapy”.

In this article, the investigators propose different mechanisms responsible of the resistance to therapy. Cancer stem cells are resistant because are protected at a molecular level by potent detoxification systems and activated mechanisms which maintain cell capacity of self-renewal. Cancer stem cells also have alterations in the resistance pathways and mechanisms for the reparation of DNA. The authors propose as a novelty that autophagy –one of the processes which control cell survival- must be included as a hallmark of cancer. In this way, they explain that autophagy can prevent that normal cell become cancerous so that if autophagy fails, this mechanism of control is lost. Autophagy is the topic for which Dr. Yoshinori Ohsumi received the Nobel Prize in Medicine in 2016.

Cancer stem cells explain why a subgroup of cancers relapse between one and five years after the end of treatment of a primary tumour. The investigators believe that once the primary tumour is treated, a group of cells –responsible of the emergence of the primary tumour- remain in the same site or closely. When the patient has respond apparently to the therapy and is recovered, this kind of cells can spread through the blood or the lymph tract and can cause the emergence of a new tumour. Thus, the relapse becomes a metastatic tumour which has built up more mutations and it is more aggressive and resistant than the primary tumour. This is when a combined therapy should be used with a targeted therapy against cancer stem cells and another therapy against tumour differentiated cells, different from the one previously used.

The group of Dr. Lleonart is now working on the mechanisms of resistance of tumorigenic cells in vitro in different kind of cancers with the aim of develop treatment which are able to revert the acquisition of this resistance. Another line of research is imitating in vivo the acquisition of the resistance in a tumour dynamic environment in animal models. For Dr. Lleonart this is a challenge in cancer research in the future.