Systemic cancer therapy includes chemotherapy (ie, conventional or cytotoxic chemotherapy), hormone therapy, targeted therapy, and immune therapy (see also Overview of Cancer Therapy). The number of available cancer therapies is increasing rapidly. The National Cancer Institute maintains an up-to-date list of medications used to treat cancer. The list provides a brief summary of each medication's uses and links to additional information.
The ideal agent would target only cancer cells and have no adverse effects on normal cells. Although older chemotherapeutic agents are often toxic to normal cells, advances in genetics and cellular and molecular biology have led to development of more selective drugs.
Most cancer medications are given systemically, usually intravenously or subcutaneously, but some are given orally. Frequent dosing for extended periods may necessitate intravenous implanted access devices (port).
Resistance to cancer therapies is common. Mechanisms include
Over-expression of target genes
Mutation of target genes
Development of alternative drug metabolic pathways
Drug inactivation by cancer cells
Defective apoptosis in cancer cells
Loss of receptors for hormones
For chemotherapy, one of the best characterized resistance mechanisms is overexpression of MDR11).
General reference
1. Bossennec M, Di Roio A, Caux C, Ménétrier-Caux C: MDR1 in immunity: friend or foe? Oncoimmunology 7(12):e1499388, 2018. doi:10.1080/2162402X.2018.1499388
Chemotherapy
Cytotoxic chemotherapy agents are classified as (1)
Other chemotherapy agents that do not fit into specific categories (eg, asparaginase)
Despite these precautions, adverse effects commonly result from cytotoxic chemotherapy. The normal tissues most commonly affected are those with the highest intrinsic turnover rate: bone marrow, hair follicles, and the gastrointestinal epithelium.
Imaging (CT, MRI, PET) is frequently done after 2 to 3 cycles of therapy to evaluate response. Therapy continues in patients whose cancer responds to the chemotherapy and in those with stable disease. In patients whose cancer progresses, the regimen is often changed or stopped.
Chemotherapy reference
1. National Cancer Institute: Major Categories of Chemotherapy Agents. SEER Training Modules. December 21, 2023.
Endocrine (Hormonal) Therapy
Endocrine therapy uses agonists or antagonists, typically to decrease the serum level of a specific hormone, to treat, to prevent recurrence, or sometimes to prevent development of cancer. It may be used alone or combined with other therapies.
Endocrine therapy is particularly useful in estrogen receptor–positive breast cancers and in prostate cancer, which grows in response to androgens. Other cancers with hormone receptors, such as endometrial cancers or some histologic types of ovarian cancer (eg, low-grade serous), are sometimes treated with endocrine therapy.
Several classes of medications with differing mechanisms are used as endocrine therapy for cancer treatment. Most endocrine therapies decrease hormone levels. One exception is the use of progestins in advanced endometrial cancer.
Endocrine therapies that decrease estrogen levels include:
Aromatase inhibitorsestrogens by inhibiting the enzyme aromatase
Selective estrogen receptor modulatorsestrogen receptors in the target malignant tissue (eg, breast); typically act as an estrogenestrogen receptor in the endometrium)
Selective estrogen receptor downregulatorsestrogen receptors in all tissues by competitive binding and downregulation of the estrogen receptor
In addition, some premenopausal women with estrogen
Endocrine therapies that decrease androgen levels include:
GnRH antagonists and agonists: Decrease GnRH secretion (agonists initially increase, but then decrease, secretion), resulting in a decrease in luteinizing hormone and follicle-stimulating hormone and subsequent decrease in testosterone production
Antiandrogens
Endocrine therapies that decrease hormone levels cause symptoms related to hormone deficiency, including hot flashes. The androgen antagonists also induce a metabolic syndrome that increases the risk of diabetes and heart disease.
Immune Therapy
Immune therapy (see also Immunotherapy of Cancer) is divided into 2 forms:
Active: Treatment is mediated by active immunity and aims to provoke or amplify a patient's anticancer immune response
Adoptive: Treatment is mediated by passive immunity and involves giving anticancer antibodies or cells
Active immune therapy can involve vaccines, modified T-cells from the patient (eg chimeric antigen receptor (CAR)-T-cells), or certain types of monoclonal antibodies that activate the patient's immune system against the cancer (eg, checkpoint inhibitors). Another example of active immune therapy is instilling bacille Calmette–Guérin (BCG) in the bladder of patients with bladder cancer.
Adoptive immune therapy often involves giving monoclonal antibodies produced in the laboratory or giving modified T cells or natural-killer (NK) cells from a healthy person to someone with cancer. Sometimes these cells are genetically modified by inserting an anticancer chimeric antigen receptor (CAR). Other forms of adoptive immune therapy include lymphokines and cytokines such as interferons and interleukins. These small signaling peptides facilitate interaction between cells involved in the immune response but are less widely used in cancer therapy.
Vaccines
More important are vaccines designed to prevent virus-related cancer. Examples include vaccines to human papillomavirus (HPV), which can prevent cervical and anal cancers (and possibly head and neck and tonsil cancers) and vaccines to hepatitis B virus (HBV), which can prevent liver cancer.
Modified T cells
In this technique, T cells are removed from the blood of a patient with cancer, modified genetically to recognize a cancer-related antigen, and reinfused into the patient. The most common example of this strategy is termed chimeric antigen receptor (CAR)-T-cells. CAR-T-cells are an effective therapy in patients with acute lymphoblastic leukemia, B-cell lymphomas, and multiple myeloma (1
Related techniques involve growing the extracted T cells in a culture and activating them by exposure to lymphokine interleukin-2 (IL-2). Alternatively, T cells may be extracted from the patient's tumor, cultured to create a larger amount, and then reinfused.
Monoclonal antibodies
Monoclonal antibodies are widely used to treat some cancers. Monoclonal antibodies can be directed against antigens that are cancer-specific or over-expressed on cancer cells. They can also be directed toward lineage-specific antigens also present on normal cells.
Some monoclonal antibodies are given directly; others are linked to a radionuclide or toxin. These linked antibodies are referred to as antibody-drug conjugates (ADCs). Some antibodies are bi-specific, with one receptor directed to a cancer-related antigen and another to an antigen on T cells. The goal is to bring T cells to the cancer to eradicate it.
Immune therapy reference
1. Cappell KM, Kochenderfer JN. Long-term outcomes following CAR T cell therapy: what we know so far. Nat Rev Clin Oncol 2023;20(6):359-371. doi:10.1038/s41571-023-00754-1
Differentiating Agents
These agents induce differentiation of cancer cells. All-transIDH2 and IDH1BCL2. Differentiating agents are ineffective in most cancers.
Angiogenesis Inhibitors
Targeted Therapies
adenosine
BRAF. This mutation is common in melanoma but also occurs in some leukemias. Another example is drugs that inhibit abnormal proteins resulting from MEK
Gene Therapy
Cancer therapy that alters genes has not been successful so far except for the development of chimeric antigen receptor (CAR)-T-cells.
Gene editing
CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 (CRISPR-associated protein 9) gene editing may be useful in some cancers alone or combined with other anticancer therapies. An example in synthetic biology is altering antigen expression on normal cells such that they are not killed by CAR-T-cell or bi-specific monoclonal antibodies. CRISPR/Cas9 gene therapy is used to treat severe sickle cell disease and transfusion-dependent beta-thalassemia.
Targeted gene therapy
Targeted gene therapy refers to therapies directed against a specific gene or gene product thought to be important in the cause or progression of a cancer rather than the anatomic site (eg, breast) or even cell type. For example, patients with a BRAF mutation might receive a BRAFBCR:ABL1). However, most cancers are caused by 10s or even 100s of mutations, making this approach considerably more complex.
Drugs directed against the FLT3IDH2IDH1VEGF and EGFR
In some hematologic conditions, such as polycythemia vera and myeloproliferative neoplasm–associated myelofibrosis, JAK2
Drugs directed against poly adenosine diphosphate (ADP) ribose polymerase (PARP) are available for BRCA
Oncolytic Viruses
More Information
The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.
National Cancer Institute's up-to-date list of agents used to treat cancer
