Bipartisan passage of the 21st Century Cures Act, signed into law December 13, 2016, by then President Obama, secures $4.8 billion in federal research funding, including funds for the Cancer Moonshot and Precision Medicine Initiative. A forward look into immunotherapy, precision medicine, and cancer prevention and disparities offers some interesting forecasting information on cancer research and treatment in 2017.
Elizabeth Jaffee, MD, on Immunotherapy in 2017
“The good news in the field of immunotherapy is that we are learning a lot more about signals tumors send to inhibit an effective immune response against them,” says Elizabeth Jaffee, MD, professor of oncology and pathology at Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center.
Jaffee explains that researchers have turned this knowledge into therapeutics that inhibit some signals (checkpoint inhibitors), so T cells can effectively attack cancer cells and developing therapeutics can activate certain cells within the tumor micro-environment (checkpoint agonists) to further activate T cells. As a result, some people have been converted from metastatic cancer patients with weeks to live into patients with chronic disease living a better quality of life. Checkpoint inhibitors are being approved for more cancer types and as first-line treatment for some cancers.
Unfortunately, these drugs only work for about 20 to 25 percent of all cancers and can unleash autoimmunity in patients who respond. Currently, side effects can be controlled in some patients with steroids. But researchers are learning more about ways to deliver these drugs in a more targeted way to circumvent toxic side effects.
In 2017, Jaffee expects to see development of new drugs that target additional immune checkpoints. One reason why almost 70 percent of cancers do not respond to checkpoint inhibitors is that cancer cells inhibit different pathways, which affect T-cell function. Therapeutics targeting immune-evasion mechanisms other than the PD-1/PD-L1 checkpoint, such as IDO, CD40, OX40, TIM-3, LAG-3 and KIR, are already in early clinical development. They will progress to clinical testing, alone or in combination with PD-1/PD-L1 drugs, and some may be approved or come close to approval this year.
According to Jaffee, other approaches for more patients to respond to immunotherapies include activating T cells using vaccines, radiation therapy or different types of immune-activating chemotherapies. Combining immune checkpoint inhibitors with agents that help uncover cancer antigens, such as PARP inhibitors that make new tumor antigens available to T cells or epigenetic agents that turn on expression of certain proteins, is another avenue. She expects to see results from such studies in 2017.
Finally, Jaffee predicts more progress this year in personalizing cancer treatment with vaccines. Tumors of many patients who respond to immunotherapy create neoantigens constantly. If researchers can identify them by sequencing tumors, they can develop vaccines to jump-start the immune system.
George Demetri, MD, on Precision Medicine in 2017
“The good news is that we are still uncovering virtually monogenic diseases – diseases that are driven by single oncogenic fusions or mutations,” says precision medicine expert George Demetri, MD, professor at Harvard Medical School and director of the Ludwig Center and Center for Sarcoma and Bone Oncology. Therapies targeting single mutations, such as NTRK fusions, lead to durable and dramatic responses.
Demetri predicts that researchers may be on the verge of putting together a composite set of predictive and prognostic biomarkers. With treatment, cancers acquire new mutations to thrive, and with technological advances scientists can track different mutations that are likely driving the disease and match them with different drugs.
Other focus areas for 2017 should include:
- Honing the ability to pick combinations that are not cross-resistant and truly synergistic or complementary;
- Seeing more efforts in developing potent epigenetic drugs;
- Gaining further understanding into smaller, molecularly defined subsets of cancer, and develop even better, more precisely targeted therapies;
- Sharing data for cancer genomic medicine;
- Realizing the importance of positive reflection on the importance of public funding of science, tied to the importance of funding investigators who can follow their instincts to make new discoveries.
Regarding provisions in the 21st Century Cures Act to roll back FDA regulations to accelerate drug development, “I like the idea that we can streamline and simplify, and have more transparency in rules for therapeutic development in cancer,” Demetri says. “I’m optimistic we will keep the focus on both safety and efficacy.”
Electra Paskett, PhD, on Cancer Prevention and Disparities in 2017
“We know a lot about how to lower one’s risk for certain cancers, but the challenge is getting people to adhere to cancer prevention behaviors at the level they should,” says cancer prevention and disparities expert Electra Paskett, PhD, professor at Ohio State University’s Division of Cancer Prevention and Control.
A recent development in the field is the ability to offer genetic testing to people to assess risk for certain types of cancer. Researchers have made significant progress, especially with tumor profiling and treatment using precision medicine approaches. “It would be really nice if we are able to apply similar approaches to understand cancer susceptibility and enhance tumor surveillance. We are getting more answers, but we are not there right now,” explains Paskett.
One of the major challenges of cancer prevention is the suboptimal uptake of HPV vaccines. HPV vaccines can potentially prevent six different cancers, yet, as of 2015, only 42 percent of girls and 28 percent of boys ages 13 to 17 had completed the recommended HPV vaccination, according to the Centers for Disease Control and Prevention (CDC) statistics.
“We [NCI-designated cancer centers] are drafting a second statement encouraging vaccination based on the recent recommendation by CDC that two shots of HPV vaccines are sufficient to provide long-term protection against certain types of HPV infections among those aged 9-14,” Paskett says.
A big concern for Paskett is that people have not embraced the HPV vaccine, which may be a byproduct of its incorrect introduction. “If we had a vaccine to prevent breast cancer, people would be lined up around the block. Unfortunately, [HPV vaccine] was not introduced as a vaccine that can prevent cancer; instead, it was introduced in relationship with sexual promiscuity, which it totally is not.”
One promising advance in the field is the ability to study tumor cells and biomarkers from blood samples. Progress is being made with technologies that can identify precancerous cells for early intervention and those that can tell a patient whether a tumor is aggressive or indolent.
With more use of precision medicine, however, researchers are likely to see the gap in disparities widen. A 2015 study on the Amenability Index has shown no disparities in mortality rates in cancers for which no effective early detection tools are available or when a cancer cannot be treated early enough to impact survival. However, disparities are striking in cancers like breast and colon where a means for early detection and precision medicine exists. “Disparities in mortality quickly emerge as you start seeing these therapies in the market because the underserved population does not have access to them,” Paskett says.
Where people live impacts cancer health disparities more than originally thought since location influences factors like crime and availability of fresh produce, besides health care, all of which impact cancer initiation and outcomes. While society may not be able to solve the problem of poverty, it can make sure people in poverty have access to good treatments and early detection, she stresses.
Support from Congress for funding the National Cancer Institute is critical for cancer research, notes Paskett. “Breakthroughs in cancer research will need everybody, including academic bodies, federal agencies and the private sector, from every area of research across the country to come together.”
- Srivani Ravoori, PhD, American Association for Cancer Research, January 6, 2017
- H.R.6-21st Century Cures Act: https://www.congress.gov/bill/114th-congress/house-bill/6