Addressing the Biggest Challenges in Stomach Cancer
Summary
- Despite an uptick in therapies and decline in the number of cases, stomach cancer is difficult to diagnose and treat.
- H. pylori increases the likelihood of cancer, and Dr. Shria Kumar hopes H. pylori screening becomes more common.
- Dr. Cindy Medina Pabon analyzes gastric tumor biomarkers to guide stomach cancer treatment.
Over the past decade, cases of stomach cancer have declined slightly but steadily in the U.S., new therapies have become available and patients’ life expectancies have ticked upward. Despite this incremental progress, stomach cancer remains difficult to catch and treat.
“I use everything in our tool belt right now to meaningfully help our patients,” said Cindy Medina Pabon, M.D., assistant lead of gastrointestinal cancer clinical research at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine. “But I don’t think it’s enough.”
However, developments in research and clinical practice offer hope that oncologists like Dr. Pabon, also an assistant professor in the Division of Medical Oncology at the Miller School, will soon have a more complete set of tools. Here’s how researchers and physicians are ensuring progress against stomach or gastric cancer continues.
Catching Tumors Early — or Preventing Them Altogether
Under the right circumstances, physicians can cure gastric cancer or even stop it before it starts. However, early detection is too often the exception, not the rule. Frequently, the malignancies are detected after they have already spread deep in the stomach’s wall and beyond.
Late diagnosis drives gastric cancer’s poor survival rate, according to Shria Kumar, M.D., a member of Sylvester’s Cancer Control Program. Gastric cancer patients are 36% as likely as the general population to be alive within five years.
Part of the problem is that symptoms, such as abdominal pain and reduced appetite, don’t attract attention for some time.
Dr. Kumar, an assistant professor in the Miller School’s Division of Digestive Health and Liver Diseases, and other gastroenterologists look for signs of cancer via an endoscopy. Currently, physicians lack specific guidelines on who should receive it and instead recommend endoscopies on a case-by-case basis.
One risk factor merits special attention: the bacterium Helicobacter pylori. Its presence increases the likelihood of cancer, and research suggests that eradicating H. pylori with antibiotics can cut the risk of gastric cancer in half.
“It’s a clear target for prevention, and prevention is always the ideal,” Dr. Kumar said.
While physicians routinely screen for infection by human papillomavirus (HPV), which causes cervical cancer, they do not regularly check patients for H. pylori. Ideally, screening would catch H. pylori infections before there is reason to suspect cancer, just as is done for HPV.
Dr. Kumar is optimistic that the field will adopt a similar preventative program for H. pylori and a strategy for catching stomach tumors in their earliest stages.
“There are a lot of studies on and a lot of attention to the questions: How do we really home in on who’s at risk? And, how do we reduce their risk?” she said.
Targeting More Molecular Changes
Although they arise in the stomach, gastric tumors are not all the same. To get a handle on the identity of a tumor, Dr. Pabon assesses its biomarkers.
With luck, these results can point her toward a specific treatment. For example, if a patient’s cancer has a distinctive pattern of changes in repetitive regions of DNA, a phenomenon known as microsatellite instability, Dr. Pabon knows that cancer will likely respond well to immunotherapy that frees the immune system to better attack the cancer.
However, many tumors don’t evince high microsatellite instability. Immunotherapy is often not effective against gastric cancer.
Currently, oncologists have a handful of other treatments tailored to certain biomarkers. These include medications developed specifically for cancer that expresses an excessive amount of the HER2 protein — a change that also drives malignancies elsewhere in the body, including breast cancer.
And more are coming online. Last October, the FDA approved zolbetuximab, the first therapy designed to treat tumors with elevated levels of the protein claudin-18.2. Meanwhile, trials of another targeted therapy, bemarituzumab, for tumors with excessive FGFR2b protein have produced promising results.
The list, however, still contains considerable gaps. Dr. Pabon estimates that at least half of her gastric cancer patients do not qualify for targeted therapy or immunotherapy. Instead, these patients can receive only chemotherapy and radiation, which are generally less effective and cause more toxic side effects.
However, she is optimistic ongoing research will lead to more options.
“In the future, I think the proportion of patients without targetable biomarkers will decline,” Dr. Pabon said.
Overcoming Resistance to Cancer Treatments
Resistance is perhaps the biggest challenge in treating gastric cancer, according to Dr. Pabon.
The time it takes to develop varies, but in general, cancer takes longer to adapt to and overcome targeted treatments and immunotherapy. But even their effects can fade, allowing drug-resistant tumors to emerge.
Researchers are working to find new options for patients facing such circumstances. A trial at the University of Miami run by Marijo Bilusic, M.D., a Sylvester researcher and oncologist who treats genitourinary cancer, is testing a combination of immunotherapies for patients whose tumors progressed and, in some cases, developed resistance after treatment with immune checkpoint inhibitors.
Oncologists also need more therapies that precisely target all a tumor’s cells and so reduce the opportunity for surviving cells to evolve resistance, according to Dr. Pabon.
Several emerging strategies for delivering drugs show promise in this regard. Some take advantage of antibodies, using them to engage immune cells to destroy cancer or to deliver therapeutic compounds into cancer cells. Researchers are also working to adapt CAR T, an immune system-based therapy now used to treat leukemia and lymphoma, to solid tumors, including gastric cancer. Developments like these bode well for the future.
“My hope is that we can find medicines that give patients more time on Earth and better quality of life,” said Dr. Pabon.
Tags: cancer research, cancer screening, Dr. Cindy Medina Pabon, Dr. Shria Kumar, gastric cancer, H. pylori infection, immunotherapy, Sylvester Comprehensive Cancer Center