The State of Care: Cancer

Gene-targeted Treatment, Minimally Invasive Techniques, Prophylactic Surgery

By Christina Hernandez Sherwood | Portraits by Jörg Meyer

Jason Wright

The patient, a woman in her early 40s and mother of two young boys, learned that her rare form of ovarian cancer had returned. But this time, her Columbia doctors recommended a treatment with less toxicity than the standard chemotherapy. Instead of targeting her cancer generally, the therapy was tailored to a specific gene abnormality in her tumor. This type of personalized treatment improves patient survival rates: Three years later, the young mother is thriving.

Columbia was one of the first academic medical centers to offer personalized, gene-targeted treatment for women’s cancers. The fight against cancer is far from over, but today the Precision Medicine Initiative for Gynecologic Cancers has more tools than ever. “The patient’s targeted therapy is something that wouldn’t have been possible 10 years ago,” says Jason Wright, MD, chief of gynecologic oncology in the Department of Obstetrics & Gynecology. “The field of oncology is moving very fast.”

No silver bullet cure exists for cancer with current medical understanding. Instead, clinicians and researchers are puncturing cancer’s armor with hundreds of softer blows, each bringing the field one step closer to vanquishing a single enemy that takes countless forms. From leading the way in precision cancer care to pioneering minimally invasive surgical techniques to offering the latest in prevention programs, VP&S faculty are stockpiling the arsenal with the latest and most effective weapons against cancer.

Perhaps the innovation closest to a cancer panacea arrived in the form of OncoTarget and OncoTreat, tests of patients’ cancer tissue samples that go beyond gene mutations. Developed by pioneering systems biologist Andrea Califano, Dr, founding chair of the Department of Systems Biology, the tests determine which transcription factors—known as master regulator proteins—will stop the patient’s cancer from progressing, no matter the original gene mutation, and which available drugs might help.

The effectiveness of OncoTarget was exemplified in the case of a 14-year-old boy whose tumors in the liver and lungs progressed despite surgery and chemotherapy. With few treatment options left for the boy, his tumor tissue was tested with OncoTarget, which identified the protein PDGFR-B as the most activated. Based on those results, his clinical team identified the best drug candidate. Two years later, the patient has had a durable response to the drug and continues the treatment with mild side effects, according to a recent study in the journal Cancer Discovery with the caveat from the authors that OncoTarget did predict the response but the mechanism is not fully understood.

Endocrine surgeon-scientist Jennifer Hong Kuo, MD, is contributing to the evolution of cancer treatment by offering patients with benign thyroid nodules an alternative to thyroidectomies. “Thyroidectomy is a straightforward operation, but it is still an operation,” says Dr. Kuo. “Patients are increasingly finding surgery disconcerting; we’re removing a perfectly healthy, perfectly functional organ that is not cancer.”

Dr. Kuo wants to expand the use of ultrasound-guided radiofrequency ablation, or RFA, a nonsurgical alternative that shrinks thyroid nodules through ablation. Dr. Kuo, director of the interventional endocrinology program in the Department of Surgery, says the percentage of these procedures at her practice has grown exponentially in recent years. As co-author of a 2022 paper in the journal Techniques in Vascular and Interventional Radiology, Dr. Kuo noted that although it is not without risk, RFA “has been shown to be a consistently safe and effective treatment for thyroid nodules with excellent long-term results.”

But not all new techniques offer the best approach for patients with cancer. Gynecologic oncologist Dr. Wright co-authored a multicenter population study published in the New England Journal of Medicine that found that minimally invasive radical hysterectomy—a widely used treatment for early-stage cervical cancer in the United States—was associated with worse patient outcomes than traditional “open” surgery.

“That was disseminated widely,” says Dr. Wright. “It changed the way we treat patients with early-stage cervical cancer surgically. At the population level, it hopefully improved outcomes for women.”

In cancer prevention, Columbia doctors are studying the effectiveness of prophylactic surgical removal of the fallopian tubes, the source of more than half of ovarian cancers, if a patient is already undergoing a hysterectomy or tubal ligation. June Hou, MD, co-director of the hereditary breast and ovarian cancer program, leads the study at Columbia.

Thanks to medical advances at Columbia and beyond, more people are surviving cancer. But sometimes treatments that save lives lead later to heart problems. Columbia established a cardio-oncology program to support and treat cancer patients and survivors. A multidisciplinary team including cardio-oncologists and imaging specialists work to control cardiovascular risk factors ahead of cancer treatment, monitor heart function throughout treatment, and work with cancer survivors who develop heart disease.

Gulam Manji

Cancer is a moving target, so beating it means staying one step ahead of its progression, says Gulam Manji, MD, PhD, director of gastrointestinal medical oncology and pancreas translational research at the Herbert Irving Comprehensive Cancer Center. Dr. Manji’s lab is digging into Columbia’s thousands of frozen pancreatic tumor samples—the pancreatic cancer surgery program at Columbia is among the highest volume centers in the country—to analyze the samples for clues about why pancreatic cancer sometimes recurs in the liver or lungs and other times never returns.

“We are not studying cells that are grown in the lab or that are from genetically engineered mice,” Dr. Manji says. “We’re analyzing tumor samples from patients who have done amazingly well and comparing them to tumors from patients who have not done so well to identify targets that can be exploited.”

Researchers separate the tumors into two groups: those from patients whose cancer recurred within 18 months and those from patients who had no recurrence after at least five years. “What is it about that tumor that makes it go to one place versus the other, and how can we exploit that finding as a drug target?” says Dr. Manji, who has patients in clinical trials. “We need to stop thinking about pancreatic cancer as one disease. We need to start thinking about it as different pathways with different clinical implications.”

Such deep, broad-ranging work is possible due to Columbia’s strong collaboration among clinicians and scientists dedicated to untangling the intricacies of cancer development and tumor microenvironment, Dr. Manji says. “In order to be smarter than the tumor, we need to try to predict what the tumor is going to do next.”

Lung Cancer Prevention

In the first six months of a comprehensive lung cancer screening program in Upper Manhattan, the team from ColumbiaDoctors and NewYork-Presbyterian diagnosed hiatal hernias, breast nodules, and a chronic lung infection—but no case of lung cancer. Nevertheless, the program’s thoracic surgeon, Bryan P. Stanifer, MD, says the program is working exactly as it should.

“We only expect about 2% of patients to have a positive test that leads to a lung cancer diagnosis,” Dr. Stanifer says. “We have had a lot of incidental findings.”

Bryan P. Stanifer

The program was inspired by the National Lung Screening Trial, which found that high-risk participants who received low-dose helical CT scans had up to 20% lower risk of dying from lung cancer than participants who received standard chest X-rays. “There’s no medication that provides that kind of result,” says Dr. Stanifer. “There was an overall survival benefit, not just lung cancer specific, of about 7%. That’s probably because we’re picking up all this other incidental stuff.”

To qualify for the Columbia lung cancer screening program, patients must meet several government-required criteria: be between the ages of 50 and 80, be a current or previous smoker, and have a smoking history of at least a pack a day for 20 years or the equivalent.

In person or via video, patients are informed of the risks—the main risk being false positives—and benefits of screening. Active smokers receive smoking cessation information, including tools and prescriptions, if appropriate. They are then scheduled for a 10-minute imaging exam, from the neck to upper abdomen, with low-dose CT, which can detect lung cancer with little radiation exposure. Patients receive their results in the mail, and the program team follows up about next steps.

Since its launch in late 2022, the program has reached about 40 referrals a month and appointments with up to 10 patients a week. Currently in place in Washington Heights, the program may be expanded to other NewYork-Presbyterian locations.

Who's Who

  • Andrea Califano, Dr, the Clyde’56 and Helen Wu Professor of Chemical Biology (in Systems Biology), professor of biomedical informatics, and professor of biochemistry & molecular biophysics (in the Institute for Cancer Genetics)
  • June Hou, MD, associate professor of obstetrics & gynecology
  • Jennifer Hong Kuo, MD, associate professor of surgery
  • Gulam Manji, MD, PhD, associate professor of medicine
  • Bryan P. Stanifer, MD, assistant professor of surgery
  • Jason Wright, MD, the Sol Goldman Associate Professor of Gynecologic Oncology