Primary liver cancer/hepatocellular carcinoma (HCC)
One of the most common forms of cancer, with a rapidly growing worldwide incidence
Primary liver cancer, otherwise known as HCC, is one of the most common and deadliest forms of cancer worldwide. It ranks as the fifth most common solid tumor cancer. The incidence of HCC is approximately 30,000 cases per year in the United States, approximately 40,000 cases per year in Europe, and is rapidly growing worldwide at approximately 800,000 cases per year. Over 85% of newly diagnosed liver cancers occur in Asia, with an incidence up to 8 times that in United States and Europe combined.
HCC has the fastest rate of growth of all cancers and is projected to be the most prevalent form of cancer by 2020. HCC is commonly diagnosed in patients with longstanding hepatic disease and cirrhosis (primarily due to hepatitis C in the United States and Europe and to hepatitis B in Asia). An estimated 90% of liver cancer patients die within 5 years of diagnosis.
The standard first-line treatment for early stage liver cancer is surgical resection of the tumor. Up to 80% of patients are ineligible for surgery or transplantation at time of diagnosis; however, early stage liver cancer generally has few symptoms, and when finally detected, the tumor frequently is too large for surgical resection. There are few alternative treatments, since radiation therapy and chemotherapy are largely ineffective. RFA (radiofrequency thermal ablation), which directly destroys the tumor tissue through the application of high temperatures administered by a probe inserted into the core of the tumor, has emerged as the standard of care for tumors up to 5 cm in diameter. Local recurrence rates after RFA treatment directly correlate to the size of the tumor. For tumors 3 cm or smaller in diameter the recurrence rate has been reported to be 10%-20%; however, for tumors greater than 3 cm, local recurrence rates of 40% or higher have been observed.
Most lethal form of gynecological malignancies among women
Ovarian cancer is the most lethal of gynecological malignancies among women, with an overall 5-year survival rate of 45%. This poor outcome is due in part to the lack of early detection strategies. Most women with ovarian cancer are not diagnosed until stage III or IV, when the disease has spread outside the pelvis to the abdomen and areas beyond and the 5-year survival rates are 25%-41% and 11%, respectively. There were approximately 22,000 new cases of ovarian cancer in the United States in 2014, with an estimated 14,000 deaths. Mortality rates have declined very little in the last 40 years, due to the lack of detection tests or improvements in treatment.
First-line chemotherapy regimens are typically platinum-based combination therapies. Although this first line of treatment has an approximate 80% response rate, 55%-75% of women will develop recurrent ovarian cancer within 2 years and ultimately will not respond to platinum therapy. Patients whose cancer recurs or progresses after initially responding to surgery and first-line chemotherapy have been divided into one of the 2 groups based on the time from completion of platinum therapy to disease recurrence or progression. This time period is referred to as platinum-free interval. The platinum-sensitive group has a platinum-free interval of longer than 6 months. This group generally responds to additional treatment with platinum-based therapies. The platinum-resistant group has a platinum-free interval of shorter than 6 months and is resistant to additional platinum-based treatments.
Pegylated liposomal doxorubicin, topotecan, and Avastin® are the only approved second-line therapies for platinum-resistant ovarian cancer. The overall response rate for these therapies is 10%-20%, with median overall survival of 11-12 months. Immunotherapy is an attractive approach for the treatment of ovarian cancer, particularly since ovarian cancers are considered immunogenic tumors. IL-12 (interleukin-12) is one of the most active cytokines for the induction of potent anticancer immunity acting through the induction of T-lymphocyte and natural killer-cell proliferation. The precedence for a therapeutic role of IL-12 in ovarian cancer is based on epidemiologic and preclinical data.
Avastin is a registered trademark of Genentech, Inc.
Glioblastoma multiforme (GBM)
Responsible for over 50% of all primary brain tumors
GBM is the most common malignant primary brain tumor. These tumors are often aggressive and infiltrate surrounding brain tissue. GBM arises from glial cells, which are cells that form the tissue that surrounds and protects nerve cells within the brain and spinal cord. GBM tumors are composed mainly of star-shaped glial cells known as astrocytes. These tumors are usually highly malignant because the cells reproduce quickly and are supported by a large network of blood vessels. They are generally found in the cerebral hemispheres, but can be found anywhere in the brain or spinal cord. GBM has an incidence of 2-3 per 100,000 adults per year, and accounts for 52% of all primary brain tumors. Overall, GBM accounts for about 17% of all tumors of the brain (primary and metastatic). They increase in frequency with age, affecting more men than women.
GBM represents the most aggressive type of tumor in the central nervous system, with only one-third of patients surviving for 1 year and less than 5% living beyond 5 years. Current treatment strategies that involve surgery, radiation, and chemotherapy address only the tumor cells. Therapies that also target the protumorigenic tumor microenvironment, which is characterized by formation of new blood capillaries and suppression of the immune system, may improve efficacy.
Leading cause of cancer deaths in the world
Lung cancer is the second most common cancer in both men and women and the leading cause of cancer deaths in the world. About 14% of all new cancers are lung cancers. Eighty percent of patients with lung cancer have smoked, but those who have never smoked can also be affected. Lung cancers are divided into small cell lung cancers (SCLC) and non–small cell lung cancers (NSCLC). Small cell lung cancers usually grow more quickly and are more likely to spread than are non–small cell lung cancers. Common treatment methods include surgery, radiation, chemotherapy, laser therapy, or a combination of these. For non–small cell lung cancers, additional treatments may include targeted therapies (such as tyrosine kinase and monoclonal antibodies to block cancer growth), photodynamic therapy, cryosurgery, and electrocautery, all aimed at destroying the tumors.
In preclinical studies, Celsion TheraSilence technology’s delivery of siRNAshort interfering RNA molecules targeting receptor 2 of vascular endothelial growth factor (VEGF)— protein critical for the growth of new blood vessels in tumors—significantly inhibited lung tumor growth.