Paving the Way for Cancer Breakthroughs

Small steps make a big impact on the lives of cancer patients and on our understanding of the disease.

A group of cancer researchers are urging doctors to focus their attention on clinical trials with ambitious goals. While finding breakthrough therapies is an admirable goal, holding out for those large steps forward ignores what we have learned from cancer genomics, the history of medical innovation and the fact that there is no one-size-fits-all therapy. Ultimately, this strategy may instead slow progress in cancer care.

In an article published in the Journal of Clinical Oncology, the American Society of Clinical Oncology called on researchers and trial sponsors and developers to design trials that aim to significantly extend the lives of cancer patients.

“Realistically, you’re just not going to get breakthroughs in common solid tumors,” Cy Stein, deputy director of clinical research at City of Hope Comprehensive Cancer Center, said. “And I don’t think that it’s going to happen in the future, because that’s what genomics is telling us.”

One advance leads to another. Although the advance might be incremental, it’s a step beyond.

As researchers unravel how mutations in our genes lead to tumors, one thing is clear: cancer is very complicated. Cancer is caused by not a single mutation but rather multiple mutations that can vary from cell to cell within a tumor. So therapies that target just one mutation might not be effective in the long-run.

Instead, many researchers and clinicians think combination therapies will be necessary. But before doctors can piece together the most effective combinations, progressive, incremental advances are needed. Together, step-by-step, these advances can lead to meaningful breakthroughs.

An excellent example is the progress in HIV treatment over the past 30 years. In 1987, researchers first developed a treatment that slowed virus growth. Then in 1995, another therapy that blocked the virus from entering a patient’s cells was introduced. The combination of these treatments dramatically improved the outlook for those infected with HIV. Today, these patients have more than 30 treatment options, which have reduced HIV death rates in the United States by more than 80 percent since the mid-1990s.

The same thing is happening for several cancers. New treatment options have added to the survival rate for cancer patients one step at a time, leading to substantial improvements over the course of decades. Take breast cancer, for example. Between 1975 and 2010, the five-year survival rate of breast cancer patients steadily improved from 75 percent to 91 percent, thanks in part to new therapies. In colorectal cancer, small incremental advances over the past two decades have contributed to the doubling of survival time for patients.


And because no two cancer patients are the same, what might be considered an incremental advance for some could be a true breakthrough for others. The success of a new therapy in a clinical trial is often measured in terms of median overall survival. “But the median—regardless of whether the trial includes 100 or 10,000 patients—is just one person right there in the middle,” Stein said. “Some patients do extraordinary well for much longer than the median. We don’t often know who they are going to be, but they are out there.”

James Bond was diagnosed with multiple myeloma in 1992, but he has been in remission for over 20 years thanks to clinical trials of new therapies. These advances have allowed him to enjoy many personal milestones long after his diagnosis.

“Our sons got married, and grandchildren arrived,” Bond wrote in a blog post. “I retired at my firm’s required age, exercised daily and became a full-time volunteer in Ohio, educating others with cancer.”

Scientists don’t yet have the knowledge to know who will gain long-term benefits from a given therapy. So only by testing those therapies in clinical trials can researchers identify those that will benefit, which can in turn improve our understanding of the biology of cancer. Trials can lead to new insights about the disease, which can lead to new targets, biomarkers and medicines and, ultimately, to identifying the right therapy for each patient.

“Advances don’t take place in a vacuum,” Stein said. “One advance leads to another. Although the advance might be incremental, it’s a step beyond.”

If we are only interested in revolutionary therapies, patients will miss out on the improvements in care that smaller advances offer. In the end, these advances can help us transform cancer into a chronic, manageable disease.