They find out how to predict the effectiveness of one of the most widely used breast cancer drugs

Precision oncology is all about knowing in advance which drug will work for a specific cancer patient, so you can provide each patient with the most effective drug for them. At the moment, these targeted therapies are only available for 5% of cancers.

A study carried out by researchers from the National Center for Cancer Research (CNIO) Miguel A. Quintela-Fandino and Silvana Mouron, together with oncology units from several Spanish hospitals, discovered a way to identify whether one of the drugs most used in conventional chemotherapy for various types of cancer, paclitaxel will be effective in each patient. The work was published by the scientific journal Nature Communications.

The so-called targeted therapy has been based, above all, on the analysis of the genetic mutations of each cancer. But research efforts around the world have revealed a unique genomic landscape for each patient. Quintela and Mouron’s research focuses on HER2-negative breast cancer, which accounts for 85% of breast cancer diagnoses and is due, in most cases, to various oncogenic mutations.

The so-called targeted therapy has been based, above all, on the analysis of the genetic mutations of each cancer

The more genes involved in the disease, the more difficult it is to know how a tumor will respond to a specific therapy. The work of the CNIO researchers is innovative because a genomic analysis (of genes) is not carried out but a proteomic analysis (of proteins). This is because in previous research, this same team had shown that even when there is a large number of oncogenic mutations, only a small number of protein alterations appear.

Scientific team participating in the study./ CNIO

Scientific team participating in the study./ CNIO

The key in two proteins: CDK4 and filamin

In other words, in most cancers, common genetic markers are not found in patients who do not respond to a particular drug, but common proteomic (protein-related) markers. Proteins are the molecules that perform most cell functions; the genes (in the DNA molecule) contain the information to make all the proteins the body needs.

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The research now published by the CNIO group analyzed samples of HER2-negative breast cancer from 130 patients treated with paclitaxel, one of the most used drugs against breast, ovarian, lung, bladder, prostate, melanoma, esophageal and other cancers.

He 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.

The work sought similarities in the expression of proteins in samples from patients who responded to paclitaxel. Two proteins specifically related to paclitaxel response were found: CDK4 and filamin.

First predictive factors

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

“We found that patients with high levels of CDK4 and filamin have a positive response rate in 90% of cases”, summarizes Quintela-Fandino, principal investigator and head of the Clinical Unit of Breast Cancer at CNIO.

We found that patients with high levels of CDK4 and filamin have a 90% positive response rate.

Miguel A. Quintela-Fandino

“The study identifies the first specific predictive factors for a conventional chemotherapy treatment, for which until now there are no predictive markers or only indirectly or imperfectly. We found that the two markers, CDK4 and filmanin A, are associated with paclitaxel activity in a very precise way”, adds this CNIO researcher.

The work is not immediately applicable to the clinic. “For what we discovered to be incorporated into the therapeutic arsenal for cancer, in addition to the industrial production of the biomarker, it would be necessary to carry out previous epidemiological and clinical studies to demonstrate its usefulness and that it improves what is already available”, concludes the scientist.

Reference:

Mouron, S., Bueno, MJ, Lluch, A. et al. “Phosphoproteomics analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.” Nat Commun

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