The best way to attack cancer tumors may be a multi-pronged approach using a combination of existing therapies, experts suggest.

Targeting drug-resistant cancer cells in a new way, by adjusting the time and sequence of cancer therapies, may be the best way to secure better treatment outcomes for people suffering from aggressive cancer, a published study says.

Cancer biologists at the Harvard Medical School, working with mathematicians from the University of Waterloo in Canada, developed a mathematical model that suggests targeting cancer cells that survive a common cancer therapy known as cytotoxic chemotherapy with a specific combination of therapies can kill those cells, reduce tumors and extend patient survival.

The researchers say they've confirmed this with lab tests involved mice with cancer.

The work could have a significant impact on cancer therapies by identifying new ways of delivering old drugs, the researchers say.

The researchers have focused on a small subset of cancer stem cells known to be drug resistant in an effort to overcome challenges associated with the failure of traditional cancer therapies.

After exposure to cytotoxic chemotherapy, populations of typical cancer cells were acquiring some attributes of the cancer stem cells, they found, by reorganizing proteins within them to overcome the cancer therapy.

However, by targeting these transitioning cells with drugs aimed at a specific protein known as Hck, large numbers of them can be killed, they determined.

Using a mathematical model helped predict the population of cells within tumors that might develop a resistance to traditional chemotherapy, they said.

"It's an exciting time to be involved in cancer biology as relationships between biologists and mathematicians are now being recognized as critical to the development of ... cancer management," says Harvard cancer biologist Aaron Goldman, who along with fellow Harvard researcher Shiladitya Sengupta authored a study published in the journal Nature Communications.

Goldman and Sengupta worked with Mohammad Kohandel, a professor in Waterloo's Department of Applied Mathematics, and Andrew Dhawan, a former Waterloo math undergraduate who is now a medical student.

"It is an honor to be a part of this important study," says Kohandel. "Application of mathematical and computational models to cancer biology is an exciting and novel area of research which can determine the most effective timing, sequencing and dosage of chemotherapy."

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