Colorectal cancer treatment: the winning combinations

October 06, 2020

Chemotherapy-based cancer treatment has distressing side effects for patients and increases the risk of developing resistance to the treatment. In an attempt to solve these problems, scientists from the University of Geneva (UNIGE) have developed a technique for quickly identifying from a large number of existing drugs the optimal synergistic combination and dose of products that can kill the tumour cells without affecting healthy cells. In partnership with the University Hospital of Geneva (HUG) and the University Medical Center in Amsterdam, they have demonstrated the effectiveness of this approach in colorectal cancer. The results are published in an article in the journal Molecular Oncology. The best drug combinations identified were assessed using in vitro tests and, for the first time, in vivo on mouse models. All the combinations were shown to be more effective than chemotherapy and did not cause any apparent toxicity in the healthy cells or in the animals. This study further paves the way for personalised, effective and safe cancer treatment.

"The technique we've designed and patented is called TGMO, which stands for phenotypically-driven therapeutically guided multidrug optimisation. It combines testing and highly-advanced statistical analysis," begins Patrycja Nowak-Sliwinska, professor at the School of Pharmaceutical Sciences of UNIGE's Faculty of Science. "It can be used to rapidly perform - in a few steps - simultaneous tests on cancerous and healthy cells (from the same patient), and evaluate all the possible combinations of drugs that we selected for the purpose. The positive synergies are preserved, while the antagonisms are rejected."

The experiment incorporated 12 drugs, all recently approved for commercialization or in the final phase of clinical trials. Colorectal cancer cell lines that had been perfectly characterised for the requirements of scientific studies were submitted to the TGMO-based "machinery". The aim of the search was to determine the combination of products closest to the desired outcome: the death of cancer cell together with an absence of effect on the healthy cell - and all using the lowest possible drug doses. The procedure resulted in multidrug combinations of three or four drugs, all slightly different from each other.

80% reduction of tumour growth

The activity of the combinations was then verified under somewhat more complex conditions than a single cell: first on a three-dimensional model of a human tumour containing cancer cells and other types, as is the case in reality, and finally on mice serving as an experimental model for colorectal cancer. The drug combinations reduced tumour growth by about 80% and consistently outperformed the effectiveness of chemotherapy. They revealed a total absence of toxicity in the healthy cells - unlike with chemotherapy - and significant activity on cancer cells freshly taken from current patients in Switzerland.

"It's the first time that in vivo tests have been carried out with drug combinations derived from our TGMO technology," enthuses Patrycja Nowak-Sliwinska. "The study shows that it is possible to efficiently identify low-dose synergistic and selective optimized drug combinations, regardless of the mutation status of the tumour, and which are more effective than conventional chemotherapy. We are currently discussing setting up a clinical study on patients so we can take things a stage further. But this stage, financing of which depends very much on the interest that a private sector might have in our approach, is first and foremost the work of clinical physicians."

Results in under two weeks

TGMO technology is designed in such a way that it achieves results in under two weeks, which is the same as the time that doctors take to determine the treatment to be administered to a patient as soon as a diagnosis has been made. "This approach clearly represents the future for oncology patients," continues Thibaud Koessler, head of Gastrointestinal Oncology in the HUG Oncology Department and one of the authors of the article. "The ability to test different drugs ex vivo and to select the combination for each patient that the cancer will be most sensitive to should increase the effectiveness of treatments while reducing the toxicity, two of the most problematic aspects in current therapies."
-end-


Université de Genève

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer 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.