Based on an article by Novid Parsi from the 果冻传媒Pulse, Fall 2022.
If it seems like there’s a groundbreaking innovation in cancer research every week, that’s because there is. New cancer drugs, immunotherapies and other innovations are now being approved at a rate of roughly three or four a month—a vast increase from the roughly 10 yearly approvals just a decade ago, according to Scientific American.
Across the board, recent decades have seen great strides in the prevention, detection and treatment of cancer. After peaking in the early 1990s, the number of U.S. cancer deaths fell 32% by 2019— from 215 deaths per 100,000 people to 146. (Smoking reduction is a large part of the decrease.) “We’re increasingly seeing the fruits of many years of innovation and dedication to research,” says Everett E. Vokes, MD, FASCO, Chair, Department of Medicine, University of Chicago.
These innovations are multifaceted, ranging from detecting and treating cancer earlier than traditional methods to leveraging the patient’s and the cancer’s biology to target tumors more directly. “That’s very different from decades ago, when cytotoxic chemotherapies were poisoning the cancer cells but also had detrimental effects to the normal cells around them,” says Jeff Allen, PhD, President and CEO, Friends of Cancer Research. Chemotherapy certainly isn’t a thing of the past, but new treatments can use it more effectively and with much less harm to patients.
With cancer detection and treatment, earlier is better. By the time a tumor is large enough to be seen on a CT scan or X-ray, it could comprise millions of cancerous cells. New treatments potentially can eradicate smaller tumors more quickly and effectively. “We’re starting to see the enhancements transition into actual treatments, and I believe this is just the beginning of what could be a sea change,” Dr. Allen says.
In short, recent innovations promise to detect and treat cancer both earlier and better. But cancer remains a major threat. This year in the U.S., more than 609,000 people are projected to die of cancer (the second most common cause of death after heart disease). Worldwide, 10 million people each year die of cancer—or nearly 1 in 6 deaths globally. “It’s been incredibly exciting to witness innovations emanating from a wide variety of academic and clinical disciplines that have had an impact on cancer in recent decades,” says Steven D. Leach, MD, Director, Dartmouth Cancer Center. Even so, experts say, not all innovations work for all cancers—or even the majority of them. Pancreatic cancer, for instance, has been particularly elusive; less than 10% of patients live beyond five years. Dr. Leach adds: “Unfortunately, a large fraction of cancer patients are unable to benefit [from these new innovations]. The bottom line is we’ve still got a ways to go.”
At the core of moving this progress forward is interdisciplinary collaborations among experts in biomedicine and other academic fields—such as the collaborations happening at the Dartmouth Innovations Accelerator for Cancer, which includes people from fields such as biomedicine, computer science and engineering. This accelerator has been developing a new type of cancer drug that could target the MYC oncogene, which contributes to many human cancers and has long been considered “undruggable.”
The work at Dartmouth—like the five promising cancer innovations below—is aiming to solve one of the medical community’s most lingering questions: Is there a future where cancer can be reasonably contained— or avoided altogether?
Targeted Therapy
Targeted therapies target tumors directly. One targeted therapy called an antibodydrug conjugate strikes only cancerous cells, not healthy cells. “It’s a bit of a magic bullet, carrying the toxin in higher concentrations to the tumor, as opposed to the rest of the body,” Dr. Vokes says. These drugs can be more effective and more tolerable.
“Antibody-drug conjugates are essentially like GPS drugs,” says Kevin Kalinsky, MD, Director, breast medical oncology, Winship Cancer Institute, Emory University. “They target a specific alteration on a cancer and then directly deliver the chemo to those cells—the way a GPS tells you where your car should go. These drugs are powerful ways of delivering treatment.”
For patients with breast cancer, one recent study used an antibody-drug conjugate to deliver a chemotherapy drug directly to the tumor. The results: The patients’ median overall survival improved by 6.6 months.
“This was welcomed by a standing ovation” at the 2022 American Society of Clinical Oncology (ASCO) meeting, says Dr. Vokes, who served as ASCO president in 2021-22. “That’s how excited people were to see that this drug can help a much larger group of patients that don’t have a high expression of HER2.” (Patients with low levels of HER2—a protein that helps breast cancer cells grow quickly—have had more limited treatment options than patients with high levels of HER2.)
Precision Medicine
Precision, or personalized, medicine considers individual patients’ genes, environments and behaviors to identify treatments that work best for them. For instance, genomic assays help determine if patients with early-stage breast cancer would benefit from chemotherapy. “We use these tests to potentially spare patients that don’t need chemotherapy and all its associated risks, toxicities and costs,” Dr. Kalinsky says.
In 2018, a groundbreaking trial called TAILORx used a genetic assay to find that the vast majority of women with node-negative breast cancer and a low-to-intermediate risk of breast cancer recurrence did not benefit from chemotherapy; they did just as well with hormone therapy. In the past, Dr. Kalinsky says, all such patients would have gotten chemo: “It was a one-size-fits-all approach. But increasingly we’re able to individualize the treatment based on the biology of the cancer.”
Immunotherapy
Immunotherapy harnesses a patient’s own immune system in the fight against cancer, so the immune system can recognize cancerous cells more readily and potentially eradicate them.
A much-heralded study, published earlier this year, involved patients with an aggressive rectal cancer that normally would need chemotherapy, radiation and surgery. These patients received a drug called a checkpoint inhibitor, which is “an agent that works by taking the brakes off a body’s own immune system,” says William L. Dahut, MD, Chief Scientific Officer, American Cancer Society. In effect, the medication uncloaks cancer cells, allowing the immune system to identify and destroy them. It was a small trial, with just 18 patients. But in all 18, the cancer completely disappeared. Experts said it was the first time in history that a study led to complete remission. More data is needed, and the results will need to be replicated. “But it shows the promise of immunotherapy if patients can have a drug treatment with manageable side effects, as opposed to chemotherapy, surgery and radiation for rectal cancer,” Dr. Dahut says. “That’s a gamechanger.”
Immunotherapy has tremendous potential, Dr. Dahut says. There probably won’t be an individual drug for each individual patient, he explains. “But we can start grouping patients together by more common cancers to make recommendations about the drugs that are available and more likely to be beneficial to them.”
Precision medicine and immunotherapy signify a bold new future for cancer treatment. “It’s going to be important over time that we empower patients to know how their own genetics might put them at risk for cancer,” Dr. Dahut says. “Knowing about your own personal genetic risk could change the way you screen for cancer or have conversations with your physician about prevention.”
Liquid Biopsy
Before cancer can be treated, it first has to be detected. Liquid biopsies, which analyze blood rather than solid tissue, have the potential to detect cancer earlier—and to save more lives.
For patients with stage 2 colon cancer, it isn’t always clear if they should or shouldn’t have chemo following surgery. Liquid biopsies could provide more definitive answers. One study, published this year, gave a group of patients with stage 2 colon cancer a liquid biopsy test to look for circulating tumor DNA (ctDNA), which are tiny fragments of a tumor’s DNA moving through the bloodstream. If the liquid biopsy test was positive,indicating the tumor’s presence after surgery, the patients received chemo; if negative, they didn’t.
This approach reduced the number of patients who received post-surgery chemo by almost half. Patients who received the ctDNA-guided treatment had a three-year, cancer-free survival rate of 92%—the same as those randomized to standard treatment.
Friends of Cancer Research has been working on a liquid biopsy initiative called the ctMoniTR Project to better understand how liquid biopsies help detect ctDNA and to determine the effectiveness of treatments that reduce ctDNA levels. “This may be even more sensitive than other modalities used to measure cancer in clinical trials,” Dr. Allen says. That’s because ctDNA found through liquid biopsies can measure cancer and response to treatment earlier than other metrics.
While healthcare providers now use blood tests to determine which treatments to use and whether cancers return after treatment, next-generation blood tests, currently in development, attempt to spot cancer or cancer risks in people who have never been diagnosed. Dr. Dahut adds a note of caution, however: “There’s obviously great potential, but we don’t want to move into a world where we tell people they have cancer or a risk of cancer, and it would never evolve clinically,” he says.
3D Imaging and Printing
Typically, breast conservation therapy aims to entirely remove the tumor from the breast while minimizing the removal of the surrounding healthy tissue. But it doesn’t always work that way. In a significant number of breast cancer lumpectomies, some of the tumor remains, often leading to mastectomy.
At Dartmouth, engineers and surgical oncologists have worked together to develop a new 3D imaging guidance system for breast surgery. They construct a 3D image of the tumor, then use 3D printing to create a guide that fits over the breast during surgery. “The surgeon ends up literally with a precise roadmap of which tissue to remove and which tissue to leave in place,” Dr. Leach says. Early results indicate this procedure, now in clinical trials, could increase the chances of successful, complete breast conservation therapy.
Prevention: Better Than the Cure?
For all the focus on treatment, prevention also would benefit from more innovation. Innovative prevention goes beyond standard measures such as tobacco cessation and obesity reduction to achieve what Dr. Leach calls “precision prevention.”
Dartmouth has pulled together experts from multiple disciplines to work on a precision prevention initiative that asks a simple yet ambitious question, Dr. Leach says: “What if we could, in an encyclopedic manner, literally catalog each and every individual’s cumulative lifetime genomic, environmental and behavioral risk factors for cancer?”
From that encyclopedia, Dartmouth hopes to come up with precision strategies to prevent cancer in groups of patients with shared risk factors. Still in its early days, the project will involve wearable tech and phone apps that record behavioral data and environmental exposure, combined with genetic sequencing followed by integration and data analysis using artificial intelligence and machine learning. “The goal is to use all these technologies to prevent cancer from ever getting started, in both current and future generations,” Dr. Leach says.
More Equitable Care
One important medical innovation doesn’t happen in the laboratory. It involves delivering more equitable cancer care—the central theme for ASCO’s 2022 annual meeting. An ASCO meeting abstract, for example, showed that higher public welfare spending was associated with decreased racial and
ethnic disparities across various types of cancer. “That tells you that social determinants of health are important in the context of innovation,” Dr. Vokes says. Cancer care must reach patients in both urban and rural settings, he adds.
“All the innovations are terrific, but if they don’t reach patients, they don’t help,” Dr. Vokes says. “Innovation is one thing, but making sure our patients worldwide have access to that innovation is important, too.”