Replacing Chemo: One-Two Drug Combo Starved Cancer Cells

Nixing cancer cells' fuel supplies may offer a new approach to treatment and may replace toxic chemo in osteosarcoma. Starving bone cancer cells could one day be an alternative to common chemotherapy drugs with severe side effects.

Osteosarcoma Explained

According to the American Cancer Society, osteogenic sarcoma or Osteosarcoma is the most common form of cancer that begins in the bones. The cancer cells in the tumors seem like early forms of bone cells that under normal conditions make new bone tissues.

Most cases of osteosarcomas are in children, teens, and young adults. Although teens are the most affected age group, osteosarcoma can develop at any age.

In 2020, Cancer.Net estimated that 800-900 people of all ages would be diagnosed with osteosarcoma, with half being children, where 2% of childhood cancers are osteosarcoma.

Standard treatment for patients diagnosed with osteosarcoma includes radiation therapy, surgery, and high-doses of chemotherapy drugs like methotrexate that can cause kidney and liver damage.

Nixing Bone Cancer Cells' Power Supply

A new study published in the journal Cell Reports describes how metabolic treatments activate the pro-survival signal of cancer cells and how two drug cocktails may lead to the death of cancer cells.

Brian Van Tine, the senior author of the study and an associate professor from Washington University, says, "We are interested in developing therapies that kill cancer cells without harming the healthy cells, potentially avoiding severe side effects of traditional chemotherapy."

He explains that the common high-dose cancer drug methotrexate can lead to liver failure and the need for dialysis. Researchers would like to rid treatments of methotrexate and replace it with metabolic therapies that would shorten the treatments, reduce side effects, and eliminate the need for multiple hospitalizations.

The Research

Scientists studied a drug called NCT-503, an investigational drug that's a member of a new class of drugs named PHGDH inhibitors that have piqued many researchers as a potential metabolic therapy for cancer.

Metabolic therapies work by targeting chemical reactions that cancer cells perform in order to sustain life. The investigational drug prevents cancer cells from being able to manufacture amino acid serine, the cell's source of energy that fuels the cancer cells' growth.

Losing serine production stops cancer cell division; however, it doesn't kill cancer.

Unfortunately, Van Tine says that osteosarcoma cells easily adapt and can turn to a different energy source.

Hence, researchers added a second drug to block the cells from adapting and burning other energy sources. Now that both serine and secondary fuel sources have been deprived, the cancer cells starved and died.

Richa Rathore, a colleague of Van Tine says, "When we added a mTORC1 inhibitor, we could control tumor growth in mice for a prolonged period of time."

Researchers are currently working on optimizing the drug treatments in the hope that findings would be taken into clinical trials. Van Tine and his colleagues hope to add more metabolic therapies in the future to eliminate chemotherapy drugs that patients often receive.

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