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 approved cancer therapies is increasing rapidly. The National Cancer Institute maintains an up-to-date list of drugs used to treat cancer. The list provides a brief summary of each drug's uses and links to additional information.
The ideal drug would target only cancer cells and have no adverse effects on normal cells. Although older chemotherapeutic drugs are often toxic to normal cells, advances in genetics and cellular and molecular biology have led to development of more selective drugs.
Most cancer drugs are given systemically, usually intravenously or subcutaneously, but some are given by mouth. Frequent dosing for extended periods may necessitate intravenous implanted access devices.
Resistance to cancer drugs 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 drugs, one of the best characterized resistance mechanisms is overexpression of MDR1, a cell membrane transporter that causes efflux of certain drugs (eg, vinca alkaloids, taxanes, anthracyclines). Attempts to alter MDR1 function and prevent drug resistance have been unsuccessful.
Chemotherapy
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 responders or patients with stable disease. In patients whose cancer progresses, the regimen is often changed or stopped.
Endocrine Therapy
Endocrine therapy uses agonists or antagonists to influence the course of cancer. It may be used alone or combined with other therapies.
Endocrine therapy is particularly useful in prostate cancer, which grows in response to androgens. Other cancers with hormone receptors, such as breast and endometrial cancers, can be controlled by endocrine therapy such as estrogenestrogens
All hormone blockers cause symptoms related to hormone deficiency, including hot flashes, and the androgen antagonists also induce a metabolic syndrome that increases the risk of diabetes and heart disease.
Immune Therapy
Immune therapy is the newest systemic cancer therapy (see also Immunotherapy of Cancer). Immune therapy is divided into two 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 antibody 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 forms 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 and head and neck and tonsil cancers) and vaccines to hepatitis B virus (HBV), which can prevent liver cancer.
Modified T cells
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.
Differentiating Drugs
These drugs induce differentiation of cancer cells. All-transIDH2 and IDH1BCL2. Differentiating drugs are ineffective in most cancers.
Anti-Angiogenesis Drugs
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
Gene therapy of cancer has not been successful so far except for the development of chimeric antigen receptor (CAR)-T-cells.
Gene editing
There is hope that 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 bispecfic monoclonal antibodies.
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 BRAFBCRABL1). However, most cancers are caused by 10s or even 100s of mutations, making this approach considerably more complex.
Recently, 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
Adjuvant and Neo-adjuvant Therapies
In some cancers with a high likelihood of recurrence after surgery and/or radiation therapy, chemotherapy drugs, hormones, and/or targeted therapy drugs are given to reduce recurrence risk even when there is no evidence of residual cancer. This strategy is effective in many cancers and is termed adjuvant therapy. Radiation therapy can also be given after surgery or chemotherapy and is referred to as adjuvant radiation therapy.
Sometimes therapy with chemotherapy, hormones, and/or targeted therapy drugs is given before definitive surgery or radiation therapy, in which instance it is termed neo-adjuvant therapy. There are several objectives of neoadjuvant therapy. One is to reduce size of the cancer, allowing for less extensive surgery and/or a smaller radiation therapy field. Another objective can be measuring response to neoadjuvant therapy and/or assessing the cancer when it is removed surgically, allowing for a more accurate prediction of the potential value of adjuvant therapy. Neoadjuvant therapy is increasingly used in breast, ovary, colorectal, lung, gastric, and other cancers. Sometimes a cancer that could not otherwise be removed by surgery is operable after neoadjuvant therapy.
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 drugs used to treat cancer
