This strategy can open new avenues to improve the effectiveness of therapies in thousands of patients who are currently being treated with classical radiotherapy or chemotherapy; the authors intend to test this approach in clinical trials
Pancreatic adenocarcinoma tumor cells showing signs of damage in the DNA of the nucleus (white dots) and micronuclei (in green), after treatment with taxol followed by CDK4/6 inhibitors. CREDIT: Centro Nacional de Investigaciones Oncologicas (CNIO)
One of the most frequent problems when treating cancer is that the tumours develop resistance to therapies, that is to say, at some point, treatments cease to be effective in stopping tumour growth. This is especially relevant in patients with aggressive diseases such as pancreatic cancer or patient with metastases, who for this reason often undergo frequent changes in treatment. Now, a study led by the Spanish National Cancer Research Centre (CNIO) in collaboration with researchers from the Weill Cornell Medicine Center and Pfizer Inc. (United States), proposes a novel combined approach to avoid pancreatic cancer resistance to chemotherapy, and thus achieve the elimination of these tumour cells effectively. The work will be published in the journal Cancer Cell.
Effective therapies in breast cancer
One of the characteristics of cancer is the alteration of the cell cycle, that is, the alteration of normal activity related to cell growth, maturation and death. The molecules CDK4 and CDK6 are involved in the uncontrolled cell growth, which ends up generating a tumour mass.
In recent years, drugs have been developed that inhibit the action of CDK4 and CDK6 and are very effective in stopping the growth of advanced breast cancer. Their clinical use, in combination with hormone therapy, has been approved in the United States since 2015 and in Europe since 2017 for patients with this type of cancer. The success of this combination has made it the standard treatment for these patients. However, until now it was not clear if these benefits could be extended to other types of cancer.
"A problem with CDK4/6 inhibitors is a consequence of their mechanism of action that prevents tumour cells from multiplying," explains Marcos Malumbres, Head of the CNIO Cell Division and Cancer Group and principal investigator of the project. "Most of the current chemotherapies -involving, for example, platinum or taxol derivatives-, act only on tumour cells that are dividing. Therefore, if we inhibit CDK4/6 and thus prevent these cells from dividing, we prevent chemotherapies from working properly. For this reason, until now it was believed that we could not combine CDK4/6 inhibitors with classical chemotherapy."
Not at the same time, but after
During her predoctoral work at the CNIO, researcher Beatriz Salvador decided to design a new strategy in which CDK4/6 inhibitors would be used not at the same time as chemotherapy, but after chemotherapy to prevent the recovery of tumour cells. The results of the study show that administering CDK4/6 inhibitors after the drugs commonly used against various metastatic tumours prevents tumour cells from resisting these treatments and growing again after chemotherapy.
Effective therapies in breast cancer
One of the characteristics of cancer is the alteration of the cell cycle, that is, the alteration of normal activity related to cell growth, maturation and death. The molecules CDK4 and CDK6 are involved in the uncontrolled cell growth, which ends up generating a tumour mass.
In recent years, drugs have been developed that inhibit the action of CDK4 and CDK6 and are very effective in stopping the growth of advanced breast cancer. Their clinical use, in combination with hormone therapy, has been approved in the United States since 2015 and in Europe since 2017 for patients with this type of cancer. The success of this combination has made it the standard treatment for these patients. However, until now it was not clear if these benefits could be extended to other types of cancer.
"A problem with CDK4/6 inhibitors is a consequence of their mechanism of action that prevents tumour cells from multiplying," explains Marcos Malumbres, Head of the CNIO Cell Division and Cancer Group and principal investigator of the project. "Most of the current chemotherapies -involving, for example, platinum or taxol derivatives-, act only on tumour cells that are dividing. Therefore, if we inhibit CDK4/6 and thus prevent these cells from dividing, we prevent chemotherapies from working properly. For this reason, until now it was believed that we could not combine CDK4/6 inhibitors with classical chemotherapy."
Not at the same time, but after
During her predoctoral work at the CNIO, researcher Beatriz Salvador decided to design a new strategy in which CDK4/6 inhibitors would be used not at the same time as chemotherapy, but after chemotherapy to prevent the recovery of tumour cells. The results of the study show that administering CDK4/6 inhibitors after the drugs commonly used against various metastatic tumours prevents tumour cells from resisting these treatments and growing again after chemotherapy.
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