Waterloo University. Canada: Controlling the time and sequence of cancer therapies may hold the
key to unlocking better outcomes for patients with aggressive cancers,
according to research published today.
In a collaborative effort between cancer biologists at Harvard
Medical School and applied mathematicians at the University of Waterloo,
researchers are now showing that improved cancer therapy can be
achieved by targeting drug-resistant cancer cells in a new way.
Dr. Shiladitya Sengupta and Dr. Aaron Goldman, cancer biologists at Harvard Medical School, led the research which is published in the journal Nature Communications. The team found that targeting cancer cells that survive a cancer therapy known as cytotoxic chemotherapy - with specific combinations of therapies - kills cancer cells in the lab, reduces tumors and extends the survival of mice with cancer.
Researchers say their findings can have a major and immediate impact
on the clinical administration of cancer therapy by introducing new
methods of delivering old drugs.
The Harvard researchers used a mathematical model developed by
Mohammad Kohandel, a professor in Waterloo’s Department of Applied
Mathematics, and Andrew Dhawan, a former Waterloo math undergrad who is
now a medical student. The model predicted the populations of cells
within tumors developing resistance to therapy.
“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,”
said Goldman.
There is a small subset of cancer stem cells (CSCs), well known to be
drug resistant, that have been of interest to researchers as they
strive to overcome the challenges associated with cancer therapy
failure. The research team found that, after exposure to cytotoxic
chemotherapy, populations of non-CSCs were acquiring some attributes of
CSCs, reorganizing the proteins within them to overcome the cancer
therapy. The researchers observed that drugs targeting a specific
protein known as Hck, killed a large fraction of these transitioning
cells.
“It is an honor to be a part of this important study," said
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.”
The lead authors are now working together with Professor Kohandel to
unravel even more complexities of cancer chemotherapy to not only
achieve better sequences and combinations of existing drugs, but to
develop brand new therapies with the use of nanotechnology.