jueves, 20 de febrero de 2020

Advances in Liver Cancer Research - National Cancer Institute

Advances in Liver Cancer Research - National Cancer Institute

National Cancer Institute

Advances in Liver Cancer Research

Vitruvian drawing of a hepatitis B virus
The hepatitis B virus (shown here) consists of DNA encased in a many-sided protein shell. Chronic infection with the hepatitis B virus can increase the risk of liver cancer. 
Credit: Jodi A. Hadden, Ph.D., University of Delaware, Newark
NCI-funded researchers are working to advance our understanding of how to prevent, detect early, and treat liver cancer in adults and children. They are also looking for biomarkers that can provide information about liver cancer, such as how aggressive it is or whether it is likely to respond to a particular therapy.
This page highlights some of the latest research in liver cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Prevention of Liver Cancer

There are several types of liver cancer in adults. The two most common types are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). HCC is the most common form of liver cancer among adults in the United States. ICC is a type of liver cancer that occurs in parts of the bile ducts within the liver.

More people in the United States are developing HCC and ICC than ever before but it’s not clear why. Researchers are trying to find the underlying causes for these trends.

Several factors can increase a person’s risk of developing HCC. Researchers are testing preventive and therapeutic strategies for some of these factors.

Cirrhosis

The biggest risk factor for HCC is cirrhosis, a disease that occurs when scar tissue forms in the liver and prevents it from working correctly. However, only 3% to 5% of people with cirrhosis will develop HCC.

Through NCI’s Phase 0/I/II Cancer Prevention Clinical Trials Program, several studies are testing whether drugs used to treat other diseases can prevent cirrhosis from advancing to liver cancer. Drugs that are being tested include green tea polyphenols, statins (cholesterol-lowering medications), and low doses of a cancer drug called erlotinib (Tarceva).

Hepatitis Virus Infection

Another common risk factor for HCC is chronic infection with hepatitis B virus or hepatitis C virus. Infection with hepatitis B virus can be prevented by vaccination, and researchers are actively developing and testing experimental vaccines for hepatitis C virus.

People with chronic hepatitis C infections may be treated with drugs that attack the hepatitis C virus itself, called direct-acting antivirals. These are used to help prevent HCC. Findings from a recent NCI-funded study suggest that treatment with direct-acting antivirals improves the survival of people with hepatitis C-related HCC.

Early Detection of Liver Cancer

Liver cancer that is diagnosed at an early stage has a good chance of being cured with surgery alone, surgery and liver transplantation, or nonsurgical treatments such as radiofrequency ablation. Researchers are working to develop tests that better detect early-stage liver cancer. They are also trying to figure out who is most at risk for liver cancer and most likely to benefit from these tests.

Surveillance

Surveillance means closely monitoring a person who has an increased risk of a disease. During surveillance, screening exams and tests are done on a regular schedule.
Some experts recommend that people who have risk factors for HCC, such as cirrhosis or chronic hepatitis B or C infection, get screened for liver cancer every 6 months. The most common screening test for liver cancer is an ultrasound exam, with or without a blood test that tests for a chemical called alpha-fetoprotein.
However, there are many challenges with these surveillance strategies and they have not been shown to prevent people from dying of liver cancer. For example, it is hard for doctors to identify which individuals are at high risk for HCC and may benefit from screening. Plus, the available screening tests are not always accurate.
Researchers from NCI's Translational Liver Cancer (TLC) Consortium are working to improve surveillance and early detection. For example, TLC-supported researchers are exploring whether electronic medical records are an efficient way to alert both doctors and patients when a patient is due for their next screening test. Another TLC study is exploring how to make HCC surveillance more personalized by matching individuals with different screening tests depending on their level of liver cancer risk.
A third TLC-supported study aims to develop a way to predict liver cancer risk for patients with cirrhosis, regardless of the cause. Nonalcoholic fatty liver disease (NAFLD) is a condition in which fat builds up in the liver. NAFLD can sometimes progress to cirrhosis. In this study, people with cirrhosis caused by NAFLD or other liver diseases are given screening tests twice a year.

Imaging

Detecting small, early-stage liver tumors with an ultrasound exam is challenging, especially for people who are obese or have cirrhosis. Scientists are developing new kinds of imaging tests that may be better at detecting small tumors.
For example, one group of TLC-funded researchers is using small molecules, called peptides, that attach specifically to cancer cells in the liver. These peptides are linked to dyes that can be seen with a CT scan or MRI.

Biomarkers

A biomarker is a molecule found in blood or other tissues that serves as a sign of a condition or disease. Scientists are working to find biomarkers in blood, urine, or other body fluids that might indicate the presence of early-stage liver cancer.
Scientists in NCI’s Early Detection Research Network (EDRN), a network of institutions researching biomarkers for early-stage cancer, have identified several promising biomarkers of early-stage liver cancer.
These biomarkers are being further studied in NCI’s HCC Early Detection Strategy Study, a long-term study of people with cirrhosis. Investigators are looking to see if these biomarkers are found in blood samples from people who developed liver cancer.
NCI is also leading a study of Baltimore, MD residents to explore genetic features of liver cancer and to determine whether molecules in people’s blood, urine, or tissues can be used as biomarkers for early detection or prevention.

Liver Cancer Treatment

Liver cancer is often diagnosed at an advanced stage. Treatment options for advanced liver cancer include targeted therapyimmunotherapy, radiation, embolization, and ablation.

Targeted Therapy

Targeted therapies are drugs or other substances that attack molecules that help cancer cells grow, divide, and spread.
For many years, sorafenib (Nexavar) was the only targeted therapy available for people with advanced liver cancer.
Several other targeted therapies have recently been approved to treat people whose liver cancer has stopped responding to sorafenib, including:
Another targeted therapy, lenvatinib (Lenvima), is now used to treat people whose liver tumors can’t be removed by surgery.
However, these treatments have not greatly improved how long people live after being diagnosed with liver cancer, so more-effective treatments are still needed.

Immunotherapy

Immunotherapy is a major focus of liver cancer treatment research. Two immune checkpoint inhibitorsnivolumab (Opdivo) and pembrolizumab (Keytruda), are currently approved to treat liver cancer.
Some examples of ongoing immunotherapy research in liver cancer include:

Radiation Therapy

NCI’s National Clinical Trials Network (NCTN) supports two ongoing clinical trials of radiation therapy for people with liver cancer that cannot be treated with surgery.
One trial is comparing proton therapy to standard photon therapy for people with HCC that cannot be removed by surgery. Proton therapy is a new kind of radiation therapy that may cause less harm to healthy tissues. People who have underlying liver disease may be able to tolerate the effects of proton therapy more than those of standard photon therapy.
The other trial is testing the combination of the targeted therapy sorafenib with a type of radiation therapy called stereotactic body radiation therapy. This approach uses special equipment to position the patient and precisely deliver radiation directly to the tumor, which may cause less harm to healthy tissues. The combination will be compared with sorafenib on its own.

Transarterial Therapy

People with advanced liver cancer can be treated with therapies that are put directly into the blood vessels that feed their tumors. For example, transarterial therapy, also called transarterial embolization, involves placing small beads into the blood vessels to cut off blood flow to the tumor.
Researchers are exploring ways to enhance transarterial therapy, such as using radioactive beads that not only block blood flow but also deliver radiation to the tumor. These therapies are also being studied in combination with targeted therapies and with immunotherapies.

Precision Medicine

Precision medicine is an approach to patient care that allows doctors to select treatments that are most likely to help patients based on the genetic alterations in their tumor.
Biomarkers that are found in tumor tissue (sometimes called tumor markers) may aid precision medicine approaches for liver cancer treatment. For instance, scientists are looking for biomarkers in HCC tumors that may help predict whether a given treatment is likely to work for an individual patient. These biomarkers could help doctors select tailored treatments for patients with HCC.
Investigators in NCI’s Center for Cancer Research are also studying the molecular features of liver tumors in detail to try to identify new drug targets and small groups of liver tumors that share similar features (called cancer subtypes). Defining more-detailed liver cancer subtypes may help guide more precise treatments for people with this disease.

Childhood and Adolescent Liver Cancer Treatment

Several types of liver cancer can develop in children and adolescents. The most common are HCC and hepatoblastoma. Adolescents are more likely to develop HCC than younger children. Standard treatments for children or adolescents with liver cancers include surgery, chemotherapy, radiation therapy, and ablation therapy.
Because childhood and adolescent liver cancer is relatively rare, randomized clinical trials of new treatments can be challenging to conduct. The Children’s Oncology Group, part of the NCI–sponsored National Clinical Trials Network, is collaborating with other institutions on the first randomized international trial for children with liver cancer, called the Pediatric Hepatic International Tumor Trial (PHITT). The trial aims to enroll more than 1,000 patients with hepatoblastoma and about 200 patients with hepatocellular carcinoma. This trial will test treatments that are adjusted by risk group and look for biomarkers of prognosis.

Adjusting Treatment by Risk Group

PHITT includes several different studies that are using patients’ risk groups to help guide new treatment approaches. A risk group reflects how likely a patient’s cancer is to come back after treatment. The trial involves multiple studies (or arms) including:
  • One study testing whether fewer cycles of cisplatin, which can cause hearing loss at its standard dose, can effectively treat children with low-risk hepatoblastoma after surgery to remove their tumors.
  • A study randomly assigning children with intermediate-risk hepatoblastoma to receive cisplatin alone or cisplatin in combination with other chemotherapy drugs. The outcomes and side effects of the regimens will be compared. The hope is that less exposure to toxic drugs will lead to fewer side effects and complications later in life.
  • A study randomly assigning children with high-risk hepatoblastoma to receive one of two different combinations of chemotherapy to see if one combination is better than the other.
  • A study testing whether children who have had surgery to remove HCC tumors benefit from receiving chemotherapy after surgery.

Biomarkers of Prognosis

PHITT also aims to identify biomarkers that indicate a child’s or adolescent’s prognosis. Trial researchers are collecting samples of participants’ blood, healthy tissue, and cancer tissue to create the world's largest repository of biological samples from children and adolescents with liver cancer.
By studying these samples, scientists have identified potential biomarkers of prognosis. If these biomarkers are found to be accurate, the researchers will use them in future studies of new therapeutic approaches.

NCI-Supported Research Programs

See a full list of liver cancer research projects that NCI funded in FY 2017.
Many NCI-funded researchers working at the NIH campus, as well as across the United States and throughout the world, are seeking ways to address liver cancer more effectively. Some research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate this basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in liver cancer.

Prevention

The Phase 0/I/II Cancer Prevention Clinical Trials Program conducts early-phase clinical trials of interventions that have the potential to prevent cancer, including liver cancer.
The Liver Cancer Pooling Project (LCPP) is an effort to pool data from different sources to study potential causes of liver cancer. Although there are several known risk factors for liver cancer, it is unclear whether these factors are responsible for the increase in liver cancer incidence in the United States. NCI investigators also use LCPP data to study factors that may protect people from developing liver cancer. For example, a study from LCPP found that people who drink coffee have a lower risk of developing HCC.
The Thailand Initiative for Genomics and Expression Research in Liver Cancer (TIGER-LC) is a consortium of researchers and clinicians from NCI and Thailand studying genetic differences between HCC and ICC, the most common form of liver cancer in Thailand. The study is designed to address liver cancer prevention, early detection, and treatment.

Early Detection

NCI’s Translational Liver Cancer (TLC) Consortium supports research to improve the early detection of liver cancer. The goals of the consortium are to better define the risks of developing liver cancer, improve surveillance for people who are at high risk of liver cancer, and improve the detection of early-stage liver tumors.

Treatment

The Liver Cancer Program is a multidisciplinary network of researchers and clinicians from across the NIH who are dedicated to improving the early detection, diagnosis, and treatment of liver cancer in adults.
NCI’s Immuno-Oncology Translational Network (IOTN) is a network of researchers who are developing new immunotherapies to treat cancer, including liver cancer.

NCI’s Fusion Oncoproteins in Childhood Cancers (FusOnC2) Consortium, part of the Cancer Moonshot, is studying the cause of fibrolamellar hepatocellular carcinoma (FLC/FLHCC) a type of liver cancer in children, adolescents, and young adults.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for liver cancer preventionscreening, and treatment.

Liver Cancer Research Results

The following are some of our latest news articles on liver cancer research:
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