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In the last 10 years, the overall cancer death rate has continued to decline. Researchers in the US and across the world have made major advances in learning more complex details about how to prevent, diagnose, treat, and survive cancer. At the forefront of emerging cancer research is the success of immunotherapy, the growing role of precision medicine, the influence that reducing health disparities can have on cancer outcomes, and the development and use of liquid biopsies and machine learning, which is allowing scientists to make sense of ¡°big data.¡± Here¡¯s a look at some of the significant advances from the past 10 years that are helping to save lives now ¨C and how PÕ¾ÊÓƵ research has contributed to each one.??

Treating Cancer Became More Precise

Precision medicine is helping move cancer treatment from one-size-fits-all to an approach where doctors can choose treatments that are most likely to successfully treat a person¡¯s cancer based on the detailed genetic information of that person¡¯s specific cancer. With advances leading to faster and less expensive gene sequencing, precision medicine is starting to be used more often to treat patients, most notably in the treatment of lung cancer. Over the last 10 years, many researchers with PÕ¾ÊÓƵ grants have contributed to that growth. For instance, PÕ¾ÊÓƵ-funded researchers across the US have developed ways to quickly analyze the large amounts of data that result from gene sequencing, identify mutations in lung cancer genes, and helped find patients when the precision drug they were using stopped working. PÕ¾ÊÓƵ also helped fund research on precision medicines for , , certain , and other types of cancer.?

Cancers Can Spread With Help From Their Neighbors

Once cancer spreads (metastasizes) from one place in the body to another, the chances of survival decrease. Until recently, scientists haven¡¯t known how much help cancer cells get from other types of cells and substances in their microenvironment. The microenvironment is the immediate area around the tumor. Over the last 10 years, PÕ¾ÊÓƵ grantees defined that must be present for metastasis to happen. They also learned more about how cancer cells:

• that change the microenvironment to ¡°clear a path¡± to the new site of spread
• change to from the immune system
• are able to
• in a new location

Identifying each ¡°helper¡± in the microenvironment could lead to new targets for novel treatments that can help shut down the cancer¡¯s growth and ability to spread.

Two New Types of Immunotherapy Were Developed

CAR T-cell therapy?(also called gene therapy) involves making changes to a patient¡¯s T cells (a type of immune cell) in the lab so they can better fight cancer. The PÕ¾ÊÓƵ helped fund some of the pioneering research involved in the (tisagenlecleucel), the first gene therapy approved by the FDA. This drug can be used to treat leukemia and lymphoma in children and adults.

Immune checkpoint inhibitors are another type of immunotherapy. They stop cancer cells from ¡°hiding¡± from the immune system. But over time, patients develop resistance to these drugs, and PÕ¾ÊÓƵ grantees are finding solutions. They¡¯ve found that:

• Certain DNA changes in melanoma tumors can
• The , the more likely it is to respond to immunotherapy¡ªespecially when it¡¯s combined with other treatments.
• Researchers can as the cancer cells adapt and stop responding to drugs.

More People Started Getting the Message that Obesity Is Linked with Cancer

Obesity is now the second-leading cause of preventable cancer deaths in the US. There¡¯s clear evidence that excess weight increases the risk for developing cancer, but research continues in order to better understand the full effect obesity has on cancer. In 2016, the PÕ¾ÊÓƵ Cancer Prevention Study-II (CPS-II) linked excess weight with . Here are some other key findings from PÕ¾ÊÓƵ research related to obesity:

• People who , including maintaining a healthy weight may lower their risk for developing cancer.
• The rates of 6 obesity-related cancers are rising faster among adults under age 50 than among older adults in the US.
• Data from the CPS-II Nutrition Survey showed that , a diagnosis of colorectal cancer was associated with an increased risk of death.
• Losing weight after age 50 may reduce a woman¡¯s risk of developing breast cancer.

Smoking Is Still the Most Preventable Cause of Cancer Deaths

Though fewer people use tobacco worldwide, smoking remains the leading cause of preventable deaths from cancer. In the past decade, PÕ¾ÊÓƵ researchers have continued on the complexities of tobacco economics, showing that reduce smoking and that increasing such taxes in states where they are still low could save lives. PÕ¾ÊÓƵ researchers also found that and are mostly myths sustained by the tobacco industry to stop public health efforts. The Surgeon General used PÕ¾ÊÓƵ data to help show the far-reaching damage from smoking includes associations with , as well as kidney failure, hypertension, infections, and respiratory diseases. In 2013, PÕ¾ÊÓƵ research showed that .

Researchers Discover More About the Microbiome¡¯s Influence on Cancer

The microbiome is a complex community of microorganisms like bacteria, fungi, and viruses that live on and in our bodies. When there¡¯s a healthy mix of these microorganisms, they do a variety of tasks like help our immune system function, and help our bodies digest food and absorb nutrients. But when the mix becomes out of balance, it may lead to disease, including cancer. Recently, researchers discovered that an unbalanced microbiome may influence metastasis, the spread of cancer to distant parts of the body. For example, in 2017, PÕ¾ÊÓƵ research found that as they metastasize. This close pairing of bacteria and cancer cells gives researchers an exciting opportunity to test whether antibiotics may help patients with Fusobacterium-associated colorectal cancer. PÕ¾ÊÓƵ research has also contributed greatly to understanding the microbiome¡¯s , especially for .

DNA Mutations Aren¡¯t the Only Causes of Cancer

Epigenetics refers to changes in how genes behave that don¡¯t involve changes to the gene itself. Put more simply, you can think of cells , and DNA as the script, which includes the stage directions about key actions. Epigenetics would be like directing. The script (DNA) may be the same, but the director is able to change the movie for better or worse. Both gene changes and epigenetic changes can be involved with cancer. In the last 10 years, PÕ¾ÊÓƵ-funded researchers have been on the forefront of epigenetics research. Some of their findings include:

• are associated with epigenetic changes.
• may be involved in cancer even when there are no genetic changes.
• Genes can be controlled by , called microRNA, that contribute to the development of a tumor and to its spread.
• may be targets for new anti-cancer drugs.

Health Equity Matters

Health equity is the idea that everyone has a fair and just opportunity to prevent, find, treat, and survive cancer. Tracking health disparities, a difference in health that¡¯s closely linked with an economic, social, or environmental disadvantages, is a way to measure progress toward achieving health equity. In the last 10 years, PÕ¾ÊÓƵ-funded research has studied a range of causes for healthcare disparities and a diverse set of health equity issues. Some of their key findings include:

• due to social and economic issues are increasing.
• States that have expanded Medicaid under the Affordable Care Act had much lower disparities among minorities, people in poverty, and those in rural areas.
• Younger, uninsured adults are more likely to be diagnosed with cancer at a later stage, when the cancer has already spread, and more likely to have financial problems related to health care.
• in the US. Structural racism refers to all the ways societies allow racial discrimination to continue though systems of housing, education, employment, earnings, benefits, credit, media, health care, and criminal justice.

New Understanding About Cancer Cells¡¯ Metabolism Opens the Door for New Drug Targets

Like normal cells, cancer cells grow by using metabolic processes to convert ¡°food¡± (carbohydrates, fats, and proteins) into energy. But cancer cells have abnormal metabolisms that help them multiply and spread quickly. Over the last 10 years, PÕ¾ÊÓƵ-funded researchers have been actively involved in work that could lead to the development of drugs that could kill cancer cells by interfering with their metabolism. Here are some of the potential new drug targets they¡¯ve discovered.

• This protein is made by a mutated gene. Normally, it keeps tumors from growing. But when the protein comes from a mutated gene, it does the opposite and helps a tumor grow. A drug that targets this protein could slow a cancer¡¯s growth.
• A type of amino acid. Amino acids are used by cancer cells to grow, and it may be particularly important for pancreatic cancer. A drug that targets this amino acid could cut off a ¡°food¡± supply to the cancer.
• The mutated genes in a cancer cell that make . This enzyme is part of the machinery cells use to turn food into energy. Drugs that target this gene in cancer metabolism may help treat some difficult-to-treat cancers, including certain brain or spinal tumors (gliomas) and cancer in the bile duct (cholangiocarcinoma).
• The that¡¯s activated in areas where there¡¯s too little oxygen. This often happens when cancer cells are growing very rapidly. A drug that targets this gene could prevent cancer from surviving in such areas.

Researchers Highlighted the Benefits of Receiving Palliative Care Early in Cancer Treatment

With cancer, there are two modes of care¡ªtreatment directed at the disease and treatment, known as palliative care, which is focused on the person with the disease. This type of care helps patients and caregivers manage symptoms from the cancer and side effects from the treatment. Clinical trials have shown that when people with cancer receive both types of treatment at the same time, their symptoms are controlled better, and they have less anxiety and depression, improved family satisfaction and quality of life, improved use of healthcare resources, and longer survival. Palliative care is one of the fastest growing areas of health care in the US, and it¡¯s changing as new treatments emerge, especially for cancer patients.

Over the last decade, PÕ¾ÊÓƵ-funded researchers led the field in publishing studies on the , finding that patients with metastatic non-small-cell lung cancer who received palliative care early in their treatment had big improvements in their quality of life and mood. A 2017 paper by an PÕ¾ÊÓƵ-grantee explained why the US needs more palliative care programs, outlining ideas for implementing . Furthermore, PÕ¾ÊÓƵ grantees helped develop an online and face-to-face curriculum to about pediatric palliative care for healthcare providers and to promote resilience as part of of children living with a serious illness.

The Future

PÕ¾ÊÓƵ has taken steps to prepare for the next decade of cancer research including developing a blueprint to improve cancer control in the US, increasing the ability for some of the best cancer experts to work together, collecting blood and tissue samples from volunteers in the PÕ¾ÊÓƵ Cancer Prevention Studies-3 (CPS-3) that will allow for more research, and starting new partnerships that can help promote more cancer research, such as with St. Baldrick¡¯s Foundation for children¡¯s cancers and the Melanoma Research Alliance. Just as researchers build on past discoveries while keeping their eyes on the future, our eyes are on our competitor¡ªcancer¡ªand on the prize¡ªa world without cancer.