Targeted Drugs for Cervical Cancer
What is cervical cancer?
Cervical cancer is a type of cancer that occurs in the cells of the cervix. According to the World Health Organization, cervical cancer is the fourth most common cancer among women worldwide. It is estimated that there were 530,000 new cases in 2012, accounting for 7.5% of all cancer deaths. More than 85% of the 270,000 cases of cervical cancer deaths occur in underdeveloped areas each year.
There are plans in developed countries to screen cervical cancer so that most precancerous lesions are discovered at a very easy stage of treatment. Cervical cancer is slow-growing, so its progression through precancerous changes provides opportunities for prevention, early detection, and treatment. Better means of detection have meant a decline in cervical cancer in the U.S. over the decades.
What causes cervical cancer?
Cervical cancer begins with abnormal changes in the cervical tissue. The risk that cause the disease is usually related to:
- Infection with human papillomavirus (HPV)
- Early sexual contact
- Multiple sexual partners
- Taking oral contraceptives (birth control pills), etc.
HPV is estimated to be the most common sexually transmitted infection in the United States. In fact, by age 50 approximately 80% of women have been infected with some type of HPV.
How to treat cervical cancer?
Surgery and concurrent chemoradiotherapy can cure 80%-90% of patients with early stage cervical cancer, but there is no satisfactory treatment for locally advanced and recurrent metastatic cervical cancer.
In recent years, the vigorous development of molecular targeted drugs has provided a new way for the treatment of advanced malignant tumors, and has also achieved certain results in the treatment of cervical cancer.
Targeted therapy for cervical cancer
- Angiogenesis inhibitors
Vascular endothelial growth factor (VEGF) secreted by different tumor cells can induce angiogenesis and lymphangiogenesis, and promote the progression of cervical precancerous lesions to invasive carcinoma. It has become an important therapeutic target for inhibiting tumor angiogenesis.
- Bevacizumab,recombinant humanized monoclonal antibody
- Sunitinib,small molecule tyrosine kinase inhibitor
- Pazopanib,inhibits VEGFR-1,2,3, PDGFR-a,b, fibroblast growth factor receptor (FGFR)-1,3, c-kit
- Imatinib, inhibitor of PDGFR the nucleus to promote cell division and proliferation.
- Epidermal growth factor receptor (EGFR) inhibitors
EGFR is a transmembrane glycoprotein with tyrosine kinase activity. Once combined with epidermal growth factor (EGF), it activates genes involved in the nucleus to promote cell division and proliferation. The EGFR signaling pathway is involved in controlling cell survival, proliferation, angiogenesis, cell movement, cell invasion and metastasis, and overexpression in most tumors.
- Cetuximab, IgG1 monoclonal antibody
- Panitumumab, specific binding to normal and tumor cell EGFR
- Gefitinib, selectively inhibits the signal transduction pathway of EGFR-TKI and blocks cancer cell growth
- Erlotinib, an EGFR-specific inhibitor with tyrosine kinase activity
- Lapatinib, with anti-HER2 activity, anti-angiogenesis
- Mammalian target of rapamycin (mTOR) inhibitors
In invasive cervical cancer, HPV infection is associated with decreased regulation of the PI3K-AKT-mTOR signaling pathway. mTOR inhibitors can reduce the expression of mTOR/4EBP1 in cells, reduce the mTOR activity of HPV-positive cervical cancer cells and the tumor burden of transplanted tumors.
- Cyclooxygenase (COX-2) inhibitiors
Cyclooxygenase is the rate-limiting enzyme in the synthesis of prostaglandins from arachidonic acid. COX-2 is an inducible enzyme that is up-regulated when cells are stimulated by various inducing factors. Celecoxib is a COX-2 inhibitor, but there is no significant advantage in clinical treatment of cervical cancer and side effects are higher than expected.
- Histone deacetylase inhibitors(HDACIs)
HDACIs inhibit the proliferation of tumor cells, induce cell differentiation and/or apoptosis by increasing the degree of acetylation of intracellular histones and increasing the expression levels of tumor suppressor genes p21, p53, etc.
In addition to the above drugs, there are many types of inhibitors in clinical research. Although molecular targeted therapy has a good effect in the treatment of some solid cancers such as lung cancer, the clinical evaluation of cervical cancer treatment has just started. With the deepening of research on the molecular targets of cervical cancer, new targeted therapies will continue to emerge, bringing new hope to patients.