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.
Classical chemotherapy is still the most common treatment for patients with metastatic cancer, not only for breast and pancreatic cancer but for most tumour types. "Being able to use CDK4/6 inhibitors to prevent tumour cells from recovering from these treatments can open new avenues for improving the effectiveness of these therapies in various types of cancer that are currently treated with classical radiotherapy or chemotherapy," Malumbres says. That is, this finding could have a positive impact on thousands of patients who are currently being treated with these therapies. "However, this strategy must be validated in the clinic. We are currently in contact with pharmaceutical companies to address this proposal in clinical trials, probably in breast and lung cancer."
Salvador-Barbero et al.CDK4/6 Inhibitors Impair Recovery from Cytotoxic Chemotherapy in Pancreatic Adenocarcinoma.Cancer Cells. Cancer Cell 2020 doi: 10.1016/j.ccell.2020.01.007 [Abstract]