chemotherapy

chemotherapy
Specialty	Oncology
MeshID	D002747

chemotherapy. It is a major category of cancer treatment that uses chemical substances to destroy cancer cells. The approach is a cornerstone of medical oncology and is often used in conjunction with other modalities like radiation therapy and surgery. Its development and application represent a significant advancement in the fight against malignant diseases.

History

The origins of this treatment modality can be traced to observations during World War I on the effects of mustard gas. Later research at Yale University led to the first use of nitrogen mustard as a therapeutic agent. A pivotal moment was the 1947 report by Sidney Farber on inducing remission in acute lymphoblastic leukemia using aminopterin, work supported by the Jimmy Fund. The subsequent development of combination regimens, such as those for Hodgkin lymphoma at the National Cancer Institute, revolutionized outcomes. The founding of the American Society of Clinical Oncology in 1964 marked the formalization of the specialty. Landmark trials, including those for testicular cancer led by Lawrence Einhorn, established curative potential for some metastatic diseases.

Types

Treatments are broadly categorized by their mechanism and origin. Alkylating agents, such as cyclophosphamide and cisplatin, directly damage DNA. Antimetabolites like methotrexate and 5-fluorouracil interfere with cellular metabolism. Antitumor antibiotics, including doxorubicin and bleomycin, are often derived from Streptomyces bacteria. Topoisomerase inhibitors, exemplified by etoposide, disrupt enzyme function. Mitotic inhibitors such as paclitaxel and vincristine target the cytoskeleton. More recent classes include monoclonal antibody therapies like rituximab and trastuzumab, developed through research at institutions like Genentech.

Mechanism of action

These agents primarily work by impairing cell division and inducing apoptosis in rapidly proliferating cells. Most target specific phases of the cell cycle, such as the S phase or M phase, to halt replication. DNA damage is a common final pathway, triggering complex signal transduction cascades that lead to programmed cell death. The effectiveness is influenced by factors like tumor heterogeneity and the microenvironment of the bone marrow. Resistance can arise through mechanisms involving the multidrug resistance protein 1 or enhanced DNA repair pathways, areas of intense study at centers like the Dana-Farber Cancer Institute.

Administration

Treatment plans, or regimens, are determined by medical oncologists based on protocols from organizations like the National Comprehensive Cancer Network. Common routes include intravenous infusion, often administered in an outpatient clinic. Other methods include oral administration, intrathecal delivery for central nervous system involvement, and intraperitoneal infusion for ovarian cancer. Dose-dense chemotherapy schedules aim to improve efficacy by reducing intervals between cycles. Supportive care during administration is critical and may involve the use of implanted ports and premedication to prevent reactions.

Side effects

Toxicity arises from the effect on normal, fast-dividing cells in tissues like the gastrointestinal tract and hair follicles. Common acute effects include myelosuppression, leading to risks of infection and anemia, and nausea and vomiting, managed with drugs like ondansetron. Mucositis and alopecia are frequent. Long-term or late effects can involve damage to the heart, lungs, or peripheral nerves, and an increased risk of secondary malignancys, such as acute myeloid leukemia. Research from the St. Jude Children's Research Hospital has been instrumental in characterizing late effects in childhood cancer survivors.

Research and development

Current efforts focus on increasing therapeutic index and overcoming resistance. The field of pharmacogenomics, explored by institutions like the Mayo Clinic, aims to personalize treatment based on genetic polymorphisms. Nanotechnology platforms are being investigated for targeted drug delivery. Development of new agents continues through large-scale screening programs at the National Institutes of Health. Significant attention is also on immunotherapy combinations, where agents are paired with checkpoint inhibitors like pembrolizumab to enhance immune response, a strategy advanced by researchers like James P. Allison at the MD Anderson Cancer Center.

Category:Oncology Category:Cancer treatments