They open a medicine that makes tumors more susceptible to chemotherapy and prevents resistance – ExamMint

Tumors more susceptible to chemotherapy
Tumors more susceptible to chemotherapy

Tumors more susceptible to chemotherapy: Many chemotherapeutic drugs destroy cancer cells by attacking your DNA, but some tumors are able to withstand because of the DNA repair pathway that allows them not only to survive, but also introduces mutations that help the cells become resistant to future treatment. Researchers at the Massachusetts Institute of Technology and Duke University have now discovered a drug compound that could block this repair path.

Tumors more susceptible to chemotherapy

“This combination of increased cell destruction with cisplatin and the prevention of mutagenesis that we expected would block this path,” says Graeme Walker, a professor of research biology at the Massachusetts Institute of Technology of the American Cancer Society (MIT), a professor at Howard Hughes Medical Institute and one of leading authors of the study.

When they treated mice with this compound with cisplatin, a drug that damages DNA, the tumors are much smaller than those treated only with cisplatin. Tumors treated with this combination cannot be expected to have new mutations that make them resistant to drugs.

Cisplatin, which was used as the first treatment option for at least a dozen types of cancer, often successfully destroys tumors, but often they appear after treatment. According to the researchers, drugs aimed at the pathway for the restoration of mutagenic DNA that contributes to this relapse can help improve the long-term effectiveness of cisplatin, but also other chemotherapeutic drugs that damage the immune system. # 39; DNA

“We are trying to make therapy better, and we also want the tumor to be regularly sensitive to repeated dose therapy,” he explains in cell paper Michael Hemann, a biology professor, member of the Institute for Integrated Cancer Research named after Koch at MIT, and lead author .

Tumors more susceptible to chemotherapy
Tumors more susceptible to chemotherapy

Cancer cells

Healthy cells have several repair paths that can accurately repair DNA damage to cells. As cells become malignant, they sometimes lose one of these precise DNA repair systems and therefore largely depend on an alternative adaptation strategy known as translesia synthesis (TLS). ,

This process, which Walker has studied for many years in various organisms, is based on specialized TLS DNA polymerases. Unlike conventional DNA polymerases used for DNA replication, these TLS DNA polymerases can essentially be a copy of damaged DNA, but the copy they make is not very accurate. This allows cancer cells to undergo treatment with a DNA damaging agent, such as cisplatin, and causes them to acquire many additional mutations that can make them resistant to further processing.

“Since these TLS DNA polymerases are indeed error prone, they are responsible for almost all mutations caused by a drug like cisplatin,” says Hehmann, “it’s well established that with the first line chemotherapy we use, if they don’t cure you, they will you are worse. ”

New inhibitor

After demonstrating that interference with the synthesis of translation may be useful, the researchers worked on finding a low molecular weight drug that could have the same effect. Researchers evaluated approximately 10,000 pharmacological compoundspotential and identified.

They tested with cisplatin on several types of human cancer cells and found that the combination destroys many more cells than cisplatin alone. And the surviving cells had a very limited ability to generate new mutations.

“Because this new translesia synthesis inhibitor aims at the mutagenic ability of cancer cells to resist therapy, it can potentially solve the problem of cancer recurrence when the cancer continues to develop due to new mutations and together represents a serious problem for cancer treatment,” they explain.

Then they tested a combination of drugs in mice with human melanoma and found that the tumors narrowed much more than cisplatin-treated tumors. Now they hope that their discoveries will lead to further research on compounds that can act as translational synthesis inhibitors to enhance the destructive effects of existing chemotherapeutic drugs and to develop variants of compounds that can be developed for potential testing in humans.



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