As a new physician treating leukemia and lymphoma patients in Japan, it didn't take long for Dr. Toshiyasu Taniguchi to spot a perplexing pattern.
At first, the anti-cancer drugs would slay unwelcome malignant cells with some success. But, inevitably, some of the cancers would come back—often with new vigor, defying the drugs that once halted them.
The phenomenon is all too familiar to many oncologists, yet its origins have remained somewhat of a mystery. Taniguchi decided he wanted to help crack the case.
"We need something new to improve the treatment of patients," he said recently in his office at the Hutchinson Center, where he joined the faculty in 2004. "The drug-resistance problem is huge."
Born in Tokyo to a semiconductor-engineer father and a science-teacher mother, Taniguchi grew up with a natural fondness for science. By the time he reached high school, all that was left to settle was which route to take: physician or researcher.
At the time, he opted for practicing medicine, believing it was "more directly related to human happiness." Soon, however, he learned that spending quality time with tiny proteins and tissue samples has its own rewards.
The crux of Taniguchi's research is a natural process called DNA repair, which scientists have suspected for many years plays a role in cancer development. If we think of DNA as a genetic blueprint, then mistakes in those vital instructions can lead to health problems. The body normally has ways of fixing these bloopers, but those repair methods can malfunction, sometimes resulting in a greater risk for diseases like cancer.
Taniguchi and his colleagues have found that a window into this process is a rare genetic disorder called Fanconi anemia, in which the majority of patients go on to develop cancer. When he was a postdoctoral researcher at Dana-Farber Cancer Institute in Boston, Taniguchi's group revealed several genes associated with Fanconi anemia form a "pathway" that interacts with two of the best-known genes associated with cancer risk, BRCA1 and BRCA2. If those genes are damaged, then breast and ovarian cancer, and other diseases are more likely to occur.
Interestingly, that same DNA damage means chemotherapy drugs, which kill cancer cells by exploiting that damage, are quite effective in most cases—at least at first. But those drugs gradually lose their effectiveness, and no one has fully understood why.
Taniguchi's lab and collaborators have discovered a particular cell event—unlike any other ever identified in relation to cancers and drug resistance—that seems to explain why popular platinum-based chemotherapy drugs like cisplatin and carboplatin fail over time to shrink ovarian tumors.
"People didn't think of this possibility before," Taniguchi said of the findings. "This phenomenon reflects that cancer cells are really creative in order to survive, and we need to be more creative than cancer cells."