Changing the treatment of cancer

July 29, 2022
Breakthroughs in the field of genomics are revolutionizing prevention, diagnosis and care.

In the last 20 years, the scientific community has made remarkable strides in diagnosing, treating and even curing cancer. Cancers that were considered a death sentence two generations ago are now treatable, with patients surviving for years, and some types of cancer can be cured without requiring patients to go through chemotherapy.

But the job isn’t done.

This year, 1,918,030 new cancer diagnoses and 609,360 cancer deaths are projected to occur in the United States, according to the American Cancer Society.

Researchers at the University of Michigan Rogel Cancer Center are working to identify and help individuals with genetic predisposition to cancer. Detailed evaluation of the genetic make-up of cancer is leading to more targeted treatments, which means longer survival and better quality of life.

At the same time, genetic testing can help identify those at greatest risk of developing cancer, enabling more interventions to prevent cancer or detect it in an earlier, more treatable phase.

The Rogel Cancer Center was also one of the first cancer centers to perform comprehensive sequencing of advanced cancer tumors, looking at DNA, RNA, and other genetic components. A panel of experts in precision oncology — researchers and clinicians — uses this information to understand what’s driving cancer and recommend the best way to treat it.

Before a cancer diagnosis

A molecular approach to cancer can also spot those trouble codes before anything goes wrong. Genetic screening can help identify those at high-risk of developing cancer based on inherited genetic factors, including people with cancer who are at risk for additional cancers.

But a Michigan Medicine study published in 2018 found nearly half of recently diagnosed breast cancer patients who were eligible for genetic testing did not get it, and a quarter of these patients were not counseled about the potential for genetic predisposition.

Genetic testing of people who have already been diagnosed with cancer can also identify potential risk for those patients’ family members. Yet it’s been challenging to trickle down genetic counseling to these potentially vulnerable relatives.

In 2020, Michigan Medicine was awarded a four million grant from the National Cancer Institute for a five year project to increase rates of genetic testing among cancer patients with personal or family histories that suggest risk for hereditary cancer syndromes.

The project is a collaboration between the Rogel Cancer Center and the Michigan Oncology Quality Consortium, a statewide network of oncology practices focused on improving the value and quality of cancer care in Michigan. Researchers will implement a family health survey for cancer patients statewide to help clinicians identify those who meet the criteria for genetic testing.

By understanding their genetic predisposition to cancer, people can pursue more frequent screening or prevention strategies to reduce their risk or detect cancer in an early, more treatable stage.

During a cancer diagnosis

Once cancer develops, genomic sequencing has led to breakthroughs in how patients are treated and opened doors to new avenues of research.

Michigan’s Oncology Sequencing Program, also known as MI-ONCOSEQ, began in 2010, making it one of the first in the nation. The program goes far beyond the capability of commercially available genetic testing kits, which look at about 150 genes.  MI-ONCOSEQ reviews more than 1,700 genes. Since launching, MI-ONCOSEQ has sequenced more than 4,000 patients’ tumors.

Among patients with advanced cancer whose therapy was informed by sequencing results, nearly 40% experienced some clinical benefit from that treatment and 20% experienced exceptionally good responses, according to a paper published in JAMA Oncology in 2021.

Another study, published in JAMA in 2015, found genetic sequencing changed the course of treatment in 46% of pediatric cancer cases at Michigan Medicine.

After a cancer diagnosis

Despite strides in reducing cancer mortality rates, some cancers don’t respond to treatment, or they grow resistant to it. For example, small cell lung cancer has a 7% five-year survival rate, according to the American Cancer Society, and certain types of breast, ovarian and prostate cancer are considered very difficult to treat right now.

But the definition of “difficult to treat” has already changed due to genomic sequencing.

In a 2017 study presented at the American Society of Clinical Oncology annual meeting, Michigan Medicine researchers showed that 72% of patients with advanced cancer could be referred for a potential targeted treatment based on a genetic marker found in their tumor.

While most patients could not enroll in those trials (their cancer was too advanced, they were too sick, or they couldn’t travel to the trial site location), 11% did, according to Erin Cobain, M.D., assistant professor of internal medicine and lead author of the 2021 JAMA Oncology paper that built on the results of the 2017 study.

Michigan Medicine is also using genomic sequencing, along with the American Society of Clinical Oncology’s Targeted Agent and Profiling Utilization Registry, orTAPUR, study, to find new treatment options for patients with advanced cancers that aren’t responding to typical drugs and treatment.

TAPUR takes genomic sequencing from tumors with many mutations and assesses whether cancer drugs previously approved for one type of cancer might also help patients with different cancer types if they have the same specific alterations to tumor DNA and RNA.

One example is in breast cancer, where immunotherapy has proven largely ineffective. But a trial that ran from 2016 to 2018 at Michigan Medicine and other sites enrolled 28 women with advanced breast cancer whose tumors had molecular changes often seen in types of cancers that respond to immunotherapy. Of those women, one-third had their tumors controlled with the immunotherapy drug pembrolizumab, and a handful saw benefits lasting more than a year.

U-M researchers are also using information from genomic sequencing to look at alterations across different kinds of cancers, and enrolling patients in “basket trials,” where those with different kinds of cancers but the same gene alterations are put into one “basket” and tested to see if a drug targeting the alteration works for them. So, a prostate cancer patient and breast cancer patient may end up in the same basket, receiving the same drug.

U of M Health release