Reducing Toxicity

Surgery, as well as treatments that are toxic to all cells, like standard chemotherapy and radiation, were the main treatments when the war on cancer began, and they are still used today. One of Duke’s contributions was making chemotherapy easier to tolerate, through clinical studies that led to the FDA approval in 1990 of a growth factor (G-CSF) that stimulates bone marrow recovery, decreasing infections and hospitalizations. “G-CSF is used all over the world now for patients getting chemotherapy,” said Michael Kastan, MD, PhD, executive director of Duke Cancer Institute and the William and Jane Shingleton Professor of Pharmacology and Cancer Biology.

Also in the 1990s, Duke made pioneering advances in stem cell transplant for patients with blood cancers. In 1992, Duke opened the nation’s first outpatient bone marrow transplantation program. High-dose chemotherapy is given on an inpatient basis, but Duke’s procedure allowed bone marrow infusions to be performed at outpatient clinics. “Patients did not have to be hospitalized, so they were able to move about more and eat better. The costs tend to be lower as well,” said Nelson Chao, MD, MBA, Donald and Elizabeth G. Cooke Professor and chief of Duke’s Division of Hematologic Malignancies and Cellular Therapy.

Today, the program has evolved to providing all follow-up care outside the clinic for bone marrow transplant patients in recovery, at their homes or an apartment near Duke. The team was the first in the world to test this practice in 2014. In 2020, in response to the COVID-19 pandemic, they made it standard of care. The practice reduces the number of people each patient is exposed to and may reduce complications and improve survival, Chao said.

Hitting the Target

Thanks to advances like these, the death rate from cancer in the United States has declined every year since 1991, according to the American Cancer Society.

Targeted therapies, which directly “hit” a specific protein or other molecule that has caused cancer to grow, have played a large role in that progress, Kastan said.

The first targeted therapy — imatinib, the drug that Moore mentioned — wasn’t approved by the FDA until 2001. Duke has made key contributions in developing other targeted therapies, including Avastin, the first cancer therapy that worked by stopping blood vessel growth, cutting off the tumor’s blood supply. In 2004, Duke clinical studies led to approval of Avastin for colon cancer,  and in 2007, Duke researchers at the Preston Robert Tisch Brain Tumor Center led studies showing that it worked for brain tumors, leading to FDA approval for that use.

In 2012, Duke breast cancer researchers led clinical trials that resulted in approval of lapatinib and trastuzumab, some of the first targeted therapies to treat metastatic breast cancer. “They both have become standard therapies for high-risk breast cancer,” Kastan said.

Despite such developments, some cancers still have low survival rates, and there still aren’t targeted therapies for most tumor types, because research is in “its infancy” in understanding the genetics of tumors, Kastan said. “We’d eventually like to stop using cytotoxic therapies, but that’s going to be a long time.”

Immunotherapies, which harness the immune system’s own ability to fight cancer, are another focus for the future. Immunotherapies that emerged beginning in 2010 have led to improved survival times for some cancers, and by 2015 they made it possible for lung cancer patients to achieve long-term survival for the first time, said Scott Antonia, MD, professor of medicine. The DCI Center for Cancer Immunotherapy, which Antonia directs, works to translate Duke discoveries into new immunotherapies, and to make these treatments work better for more patients.

The Right Treatment for the Right Patient at the Right Time

No matter the type of treatment, the future of cancer care will continue to move toward precision medicine, or “finding the right treatment for the right patient at the right time,” Kastan said. This includes choosing  treatments based not only on the genetics of the tumor, but also on the genetics, age, and risk factors of each patient.

Duke has made some inroads with a Molecular Registry of Tumors that stores information about mutations in patients with advanced cancers, uses Duke-created software to match patients with treatments that may work best for their tumor, then notifies doctors automatically. In addition, Duke researchers in prostate cancer and colorectal cancer have in the last three years led clinical trials showing that a “liquid biopsy” can be used to track how tumors are evolving and responding to treatment, Kastan said. Liquid biopsies use a blood test to detect circulating tumor cells or tumor DNA, so they are less invasive and faster than traditional tissue biopsies.