CNIO researchers discover how to predict

• This is the first time that a biomarker can accurately predict the effectiveness of conventional chemotherapy treatment.

• The study published in Nature Communication was performed on samples of HER2-negative breast cancer, which accounts for 85% of diagnosed breast tumours.

• “Patients with high levels of CDK4 and filamin proteins have a positive response rate in 90% of cases,” explains Miguel A. Quintela-Fandino, head of the CNIO’s breast cancer clinical unit.

Precision oncology aims to determine which drug is likely to work in each cancer patient. Currently, these targeted therapies are only available for 5% of cancers. The study conducted by CNIO researchers Michael A. Quintela-Fandino and Silvana Mouronin collaboration with oncology units of several Spanish hospitals, discovered a way to identify whether one of the most commonly used drugs in conventional chemotherapy for various types of cancer, paclitaxel, will be effective in every patient. The book was published in Communication Nature.

Targeted therapies are mainly based on the analysis of genetic mutations in each cancer. Quintela and Mouron’s research focuses on HER2 negative breast cancerwhich accounts for 85% of breast cancer diagnoses and is due, in most cases, to not a few but many oncogenic mutations – designing targeted therapies based on genetic mutations for this tumor is therefore a difficult goal to achieve.

Quintela and Mouron did not, however, do a genomic analysis (of the genes), but a proteomic analysis (of proteins). They had shown in previous research that even when a large number of oncogenic mutations are present, only a small number of protein alterations appear.

Two proteins, CDK4 and filamin, predict response to paclitaxel

In other words, while in most cancers no common genetic markers are found in patients who are unresponsive to a given drug, common protein-related markers can indeed be found. Proteins are the molecules that perform most of the functions of cells; the genes (in the DNA molecule) contain the information to produce all the proteins needed by the body.

The CNIO group has analyzed HER2-negative breast cancer samples from 130 patients treated with paclitaxel, one of the most widely used drugs against breast, ovarian, lung, bladder, prostate, melanoma, esophageal and other cancers. They looked for similarities in protein expression in samples from patients who responded to paclitaxel and found two proteins specifically linked to the response to paclitaxel: CDK4 and Filamin.

“Early predictors of response to conventional chemotherapy”

The researchers showed that this association appears when paclitaxel is used, but not when other drugs are used.

“We found that patients with high CDK4 and filamin levels have a positive response rate in 90% of cases”, summarizes Miguel A. Quintela-FandinoPrincipal Investigator and Head of CNIO Breast Cancer Clinical Unit.

“The study identifies the first specific predictors of conventional chemotherapy treatment, for which only indirect or imperfect predictive markers have been known until now. Instead, CDK4 and filmanin A are associated with the activity paclitaxel in a very precise way”, adds this CNIO researcher. .

The work is not immediately applicable to the clinic. “For this discovery to be integrated into the oncological therapeutic arsenal, epidemiological and clinical studies would have to be carried out”, specifies Quintela-Fandino.