IDIBELL researchers relate the amplification of a chromosomal region with resistance to to a chemotherapeutic drug in breast cancer

June 18, 2019

Researchers at the Bellvitge Biomedical Research Institute (IDIBELL), with the participation of collaborators from the Baylor College of Medicine (Houston) and the University Institute of Oncology of Asturias (IUOPA), publish today in Cancer Research a study where they relate the high number of copies of a chromosomal region with the appearance of resistance to a chemotherapeutic drug. The research was led by Dr. Eva González-Suárez, head of the Transformation and Metastasis group at IDIBELL.

Nowadays, chemotherapy, despite its side effects, remains the most efficient treatment to fight cancer. One of the most widespread drugs in chemotherapy, and which has been the subject of this study is docetaxel, a chemical compound that acts on tumor cells preventing their proper division. The research project has focused on the most aggressive subtype of breast cancer: the triple negative breast cancer (TNBC). This subgroup is characterized by being quite heterogeneous (reason why there are no targeted therapies to combat it) and it is usually associated with poor prognosis. Despite promising initial responses to chemotherapy, resistance to the drug often develops during the treatment. One of the challenges that oncologists face is the selection of the chemotherapy drug that will benefit patients with triple-negative breast cancer. This selection is made in most cases arbitrarily.

To carry out this study, scientists have worked with patient derived xenografts (PDXs). These PDXs are animal models (mice) in which tumor cells from the patient have been implanted, so that the tumor sample is much more representative than a conventional cell culture. These models can be used to test the efficiency of drugs as well as to study the processes of emergence of chemoresistance that is, to understand how tumor cells become unresponsive to treatments.

Analyzing the effect of docetaxel in triple negative breast cancer in PDXs, researchers have observed that as in patients, resistance to docetaxel emerges during treatment and have compared the genome of matched tumors sensitive to docetaxel and their counterparts that developed resistance upon continuous drug exposure. They have identified an increase in the number of copies of a region of chromosome 12, called chr12p, in tumors resistant to docetaxel and even after short treatments with docetaxel. These results imply that a subpopulation of tumor cells resistant to docetaxel is present in the tumors and survive the drug, unlike the others that die during treatment.

In addition, researchers have discovered that this subpopulation with multiple copies of chr12p resistant to docetaxel is very vulnerable to treatment with another chemotherapeutic drug, carboplatin, which is why Dr. González-Suárez proposes "applying a sequential treatment that combines first docetaxel and then carboplatin, instead of using both drugs individually or simultaneously as it is currently done. "

"We have associated the presence of this amplified chr12p chromosome region to emergence of docetaxel resistance and carboplatin vulnerability," says Dr. Eva González-Suárez. "We propose that the copy number of chr12p is considered as a biomarker to predict whether patients' tumors will develop, or not, docetaxel resistance; and what is even more important, once docetaxel resistance emerges, to have an alternative drug to treat the patients, carboplatin.

This discovery could represent the first description of a biomarker for the selection of the chemotherapy drug and the sequence of treatments that could benefit patients with triple negative breast cancer.
-end-


IDIBELL-Bellvitge Biomedical Research Institute

Related Chemotherapy Articles from Brightsurf:

Chemotherapy is used to treat less than 25% of people with localized sarcoma
UCLA researchers have found that chemotherapy is not commonly used when treating adults with localized sarcoma, a rare type of cancer of the soft tissues or bone.

Starved cancer cells became more sensitive to chemotherapy
By preventing sugar uptake, researchers succeeded in increasing the cancer cells' sensitivity to chemotherapeutic treatment.

Vitamin D could help mitigate chemotherapy side effects
New findings by University of South Australia researchers reveal that Vitamin D could potentially mitigate chemotherapy-induced gastrointestinal mucositis and provide relief to cancer patients.

Less chemotherapy may have more benefit in rectal cancer
GI Cancers Symposium: Colorado study of 48 patients with locally advanced rectal cancer receiving neoadjuvant chemotherapy, found that patients receiving lower-than-recommended doses in fact saw their tumors shrink more than patients receiving the full dose.

Male fertility after chemotherapy: New questions raised
Professor Delb├Ęs, who specializes in reproductive toxicology, conducted a pilot study in collaboration with oncologists and fertility specialists from the McGill University Health Centre (MUHC) on a cohort of 13 patients, all survivors of pediatric leukemia and lymphoma.

'Combo' nanoplatforms for chemotherapy
In a paper to be published in the forthcoming issue in NANO, researchers from Harbin Institute of Technology, China have systematically discussed the recent progresses, current challenges and future perspectives of smart graphene-based nanoplatforms for synergistic tumor therapy and bio-imaging.

Nanotechnology improves chemotherapy delivery
Michigan State University scientists have invented a new way to monitor chemotherapy concentrations, which is more effective in keeping patients' treatments within the crucial therapeutic window.

Novel anti-cancer nanomedicine for efficient chemotherapy
Researchers have developed a new anti-cancer nanomedicine for targeted cancer chemotherapy.

Ending needless chemotherapy for breast cancer
A diagnostic test developed at The University of Queensland might soon determine if a breast cancer patient requires chemotherapy or would receive no benefit from this gruelling treatment.

A homing beacon for chemotherapy drugs
Killing tumor cells while sparing their normal counterparts is a central challenge of cancer chemotherapy.

Read More: Chemotherapy News and Chemotherapy Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.