Classes of drugs used in chemotherapy
Chemotherapy uses various types of drugs, which vary in target (target) and mechanism of action. Based on these two criteria, chemotherapy drugs can be classified as follows:
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Alkylating agents: these compounds act by forming bonds with DNA, which prevent its replication and, secondarily, alter its transcription into RNA. In this way they cause the blocking of protein synthesis and the cell undergoes the defined programmed death mechanism apoptosis.
Alkylating agents are dose-dependent, i.e. the percentage of cancer cells that die is directly proportional to the amount of drug used.
They belong to this category:- nitrogenous mustards: such as chlorambucil and melphalan, used, respectively, in the treatment of leukemia and myeloma;
- the nitrosoureas: such as carmustine and lomustine used in the treatment of brain tumors and Hodgkin's lymphoma;
- the platinum derivatives: such as cisplatin, used in the treatment of ovarian, testicular and advanced bladder cancer.
- Antimetabolite agents: these drugs interfere with the synthesis of DNA, inhibiting the formation of nucleotides (the units that compose it). If the nucleotide intermediates cannot be synthesized, DNA synthesis is definitively stopped and tumor growth arrested. Furthermore, many of these molecules have a structure very similar to that of endogenous nucleotides (the normal nucleotides present in the cell) and can replace them in the new DNA chain, preventing their correct formation. They belong to this category:
- the 5-fluorouracil, used in the treatment of colon and stomach cancer;
- the methotrexate, a folic acid synthesis inhibitor, used in the treatment of breast, head, neck and certain types of lung cancer and non-Hodgkin's lymphoma.
- Antimitotic agents: these drugs act during the cell division phase (mitosis), in particular in the phase in which the newly synthesized DNA must be divided between the two daughter cells. The breakdown of genetic material between cells occurs thanks to mitotic spindle, a complex structure made up of particular proteins called microtubules.
Many of these drugs are derived from natural molecules that were first isolated from plants. The best known classes of drugs belonging to this category are the Vinca alkaloids and taxanes.
- The Vinca alkaloids they act by preventing the formation of microtubules and the aforementioned mitotic spindle; they can be of both natural and synthetic origin. Among those of natural origin are vincristine and vinblastine, isolated for the first time from Catharantus roseus (otherwise known as Madagascar periwinkle).
Vincristine is used in the treatment of acute leukemia and various types of Hodgkin and non-Hodgkin lymphomas; Vinblastine is useful in the treatment of advanced testicular cancer and Kaposi's sarcoma.
Among the synthetic derivatives is vinorelbine, used - alone or in combination with cisplatin - for the treatment of non-small cell lung cancer.
- THE taxanesinstead, they perform an "opposite activity, that is, they prevent the disassembly of microtubules and the mitotic spindle. This class includes the natural molecule paclitaxel, isolated for the first time from the bark of a Pacific conifer (Taxus brevifolia); it is used in the treatment of breast, lung and ovarian cancer.
Its semi-synthetic derivative is docetaxel, used against breast, lung and prostate cancer.
- The Vinca alkaloids they act by preventing the formation of microtubules and the aforementioned mitotic spindle; they can be of both natural and synthetic origin. Among those of natural origin are vincristine and vinblastine, isolated for the first time from Catharantus roseus (otherwise known as Madagascar periwinkle).
- Inhibitors of topoisomerase I and II: topoisomerases I and II are enzymes that play a fundamental role in the winding and unwinding of the DNA double helix during its transcription or replication.
The epipodophyllotoxins, which are the semi-synthetic derivatives of podophyllotoxin, a molecule that is extracted from the dry roots of the plant Podophyllum peltatum.
Epipodophyllotoxins inhibit type II topoisomerase (i.e. they hinder its normal functioning). Among these molecules, etoposide stands out, used in the treatment of lung cancer and Burkitt's lymphoma.
On the other hand, type I topoisomerase is inhibited by campothecins. The progenitor of this class of drugs is the natural molecule campothecin, isolated for the first time from the bark of Camptotheca acuminata. Research carried out on this molecule has led to the synthesis of its semisynthetic derivatives, including topotecan, used in the treatment of ovarian cancer and small cell lung cancer when the first-line treatment is ineffective. - Cytotoxic antibiotics: the antibiotics used in chemotherapy are able to block the transcription of DNA by inducing mutations within it and / or by inhibiting fundamental enzymes involved in its replication process.
The anthracyclines, including doxorubicin and daunorubicin.
Doxorubicin is used for the treatment of haematological cancers, solid cancers of the breast, ovaries, bladder, stomach and thyroid.
Daunorubicin is used for the treatment of lymphocytic and non-lymphocytic leukemias.
The mechanisms with which anthracyclines act are multiple, since they are able to intercalate (insert) inside the double strand of DNA, to generate very reactive free radicals, which damage the molecules present inside the cells, and to inhibit type II topoisomerase.
Other cytotoxic antibiotics used in chemotherapy are actinomycin, bleomycin and mitomycin.
- L"actinomycin it is a complex molecule capable of intercalating itself in DNA preventing the synthesis of RNA. It is used to treat Wilms tumor (or neuroblastoma, a type of adrenal tumor), testicular cancer and rhabdomyosarcoma (malignant tumor that develops in connective tissues).
- There bleomycin it is a natural molecule isolated for the first time from the bacterium Streptomyces verticillus. It is able both to intercalate in DNA and to damage it thanks to the formation of extremely reactive free radicals. It is used for the treatment of Hodgkin's lymphoma.
- There mitomycin it performs the same function as the alkylating agents: therefore it establishes bonds with the DNA preventing its replication; moreover, it is capable of producing cytotoxic free radicals. It is used in the treatment of stomach, pancreatic and bladder cancer.
- L"actinomycin it is a complex molecule capable of intercalating itself in DNA preventing the synthesis of RNA. It is used to treat Wilms tumor (or neuroblastoma, a type of adrenal tumor), testicular cancer and rhabdomyosarcoma (malignant tumor that develops in connective tissues).
Other chemotherapy approaches
Hormone therapy
Hormones are mainly used for neoplasms involving organs and tissues that are sensitive to them. Examples of these conditions are estrogen-dependent breast cancer, endometrial cancer and metastatic prostate cancer, whose growth depends on the presence of sex hormones.
The antiestrogens (for example, tamoxifen), i progestogens (for example, megestrol acetate) and gli antiandrogens (eg, flutamide) are used to treat hormone-dependent cancers and are often used after surgery, radiotherapy and / or other chemotherapy.
THE glucocorticoids (such as prednisone and methylprednisolone) are commonly given together with anticancer agents to suppress lymphocytic activity and attempt to increase the likelihood of success in treating leukemia and lymphoma.
In other cases, hormones can be used as carriers (ie as a vehicle) for anticancer drugs; this is the "example of"estramustine. This drug derives from the union of a nitrogenous mustard (a alkylating agent) with the "hormone estradiol; the latter" is used as a vector to ensure that the drug is distributed, selectively and specifically, in the prostate tissue. Estramustine is used for the palliative treatment of progressive prostate cancer.
Enzymatic therapy
This type of approach involves taking enzyme supplements as an alternative form of cancer treatment. However, there is no solid scientific evidence that this therapy is effective.
Enzymes are particular natural proteins, produced by cells, essential for the metabolic processes that take place in the organism.
The first to introduce this type of approach was the Scottish embryologist John Beard in 1906, who proposed the use of pancreatic enzymes for the treatment of pancreatic cancer.
Subsequently, various researches were carried out, both in America and in Europe, but none of these managed to demonstrate the real effectiveness of the therapy.
An "exception seems to be the administration of L-asparaginase (an enzyme capable of metabolizing the amino acid asparagine). This drug has been approved for use as an adjunct to other chemotherapy therapy.
Exogenous asparagine (not produced by the body but taken, for example, with food) is an essential amino acid for the growth of malignant lymphocytic leukemia cells, since these do not have the enzymes necessary to synthesize it. Healthy cells, al on the contrary, they possess all the enzymes necessary for its synthesis.
The therapeutic strategy consists in administering the L-asparaginase enzyme, which degrades the exogenous asparagine thus depriving the cancer cells of a molecule that is indispensable for them. Healthy cells, on the other hand, being able to produce it independently, are able to withstand the therapy.
Future prospects
Due to the numerous and important side effects caused by chemotherapy and the increasingly frequent development of resistance to treatments by cancer cells, the search for new and innovative drugs is constantly growing.
The aim of the research is to obtain drugs that are specifically and selectively effective for malignant cells, and that are not subject to the phenomenon of multi-drug resistance.
In this regard, the so-called hybrid drugs. These drugs consist of a "single molecule, obtained by binding together two or more drugs that have all, or only some, anticancer activity. The potential advantages, compared to cocktail-based combination antineoplastic chemotherapy, can be:
- Possible reduction of toxicity;
- Better targeting of one or more components towards the therapeutic target (the target of anticancer therapy), thanks to the characteristics of one of the elements that make up the hybrid drug;
- Possible inhibition of the onset of the phenomenon of resistance to chemotherapy, while maintaining the activity of each individual component;
- Better predisposition on the part of the patient, who has to take fewer medicines.
