Drugs used in cancer

Intercalate betureen chlormethine cyclophosphamide chlorambucil busulphan 

Many drugs (above) are cycle specific i.e. non-phase specific 

The uim of trcutmeni iti pm tents with cancer is cure or. if this is not prissible. effective paJliiition. Many cancers present as locali/cd tumour musses, but surjiery or radiotherapy ol len fails to eradicate the disease, which eventually becomes widespread. For this reason, there is a trend to incorponile systemic treatment with local treatment at the time of diagnosis, 

Aniicanccr drugs are classified according to their sites of action along the synthetic pathway of cellular macromolecules (top). Some drugs are only effective during part of the cell cycle (phase-specific drugs, left). 

Pacliiaxd with cisplaiin or carboplaiin b the treatment of choice in ovaritm cancer. Pretreaimeni with dexameiha.sone and anithbiamines is necie.ssaiy to prcvem scnsitiviiy reactions. 

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The antitumor agent compound 593 A, was isolated from Streptomyces griseoluteus. This compound possesses the /3-chloramine function of the nitrogen mustards, a group of compounds whose derivatives have been incorporated into many synthetic drugs used in cancer chemotherapy. ... 

Many drugs used in cancer chemotherapy inhibit DNA synthesis or function... 

Cancer cells typically overexpress ATP-dependent transmembrane transporters capable of expelling a wide variety of chemically unrelated drugs used in cancer therapy. This phenomenon is known as multidrug resistance (MDR). Inhibition of MDR proteins, such as the P-glycoprotein (Pgp), to prevent drug efflux during cancer therapy has thus potential clinical value. 

Mechanism of Action. Although the exact mechanism of azathioprine is unknown, this drug probably interferes with DNA synthesis in cells mediating the immune response. Azathioprine appears to act like the antimetabolite drugs used in cancer chemotherapy (see Chapter 36). The cell normally uses various endogenous substances such as purines as ingredients... 

Nearly all pharmaceutical products must be processed under strict aseptic conditions and be protected from outside contamination. In addition, as is the case for an-timinotic drugs used in cancer therapy, some products are toxic, such as cytostatica, and should not be released into the environment. Bulk freeze-drying is best done within a controlled, confined container that in turn does not hinder processing. 

Drugs used in cancer chemotherapy are cytotoxic drugs, hormones, plant derivatives, radioactive isotopes, and miscellaneous agents (e.g., procarbazine, hydroxyurea, mitotane). The plant-based drugs vincristine, vinblastine, vinorel-bine, etoposide, and campothecins. Radioactive isotopes, such as 131 iodine (131 I), are used in the treatment of thyroid tumors. Cytotoxic drugs (e.g., cis-platin, cyclophosphamide, 6-mercaptopurine, 5-fluorouracil, and methotrexate are used for the treatment of cancer. 

Among the drugs used in cancer chemotherapy, we may broadly distinguish two functional groups ... 

SAFETY PROFILE Confirmed carcinogen producing liver mmors. An experimental teratogen. A drug used in cancer treatment. When heated to decomposition it emits toxic fumes of POx. See also ESTRADIOL, ESTERS, POLYMERS, and PHOSPHORIC ACID. 

These nucleoside-derived drugs show slight structural modifications with respect to natural nucleosides thus, CNT and ENT are strong candidates to mediate the translocation of these compounds. However, the hypothesis that transporters belonging to the same gene family are responsible for the uptake of structurally related compounds is valid for nucleoside-derived drugs used in cancer therapy but not for all antiviral treatments. 

A substance inhibiting cell growth by competing with, or substituting for, a natural substrate in an enzymatic process. Sulfonamides and trimethoprim are antimetabolites, as are many antiviral agents and drugs used in cancer chemotherapy. 

PROBLEM 27.21 5-Fluorouracil is a drug used in cancer chemotherapy. What is its structure ... 

This chapter will concentrate on the drugs used in cancer chemotherapy with consideration of some of the other forms of therapy. 

Sulfonamides and trimethoprim are antimetabolites, as are many antiviral agents and drugs used in cancer chemotherapy. 

The investigation of DNA-dmg interactions and the development of a fast and accurate electrochemical method for the detection of DNA oxidative damage. Fig. 6.3, especially from anticancer drugs used in cancer therapy or in the development of new antineoplasic drugs, has been growing in recent years because DNA-electrochemical biosensors are a very good model for simulating nucleic acid interactions and to clarify mechanisms of action. 

Cancer cells can develop resistance to the anticancer drugs used in cancer therapy. Furthermore, the cells become resistant to other chemotherapeutic drugs whose structures and functions are unrelated. This phenomenon is called multidmg resistance (MDR) [58, 59]. MDR is multifactorial, but P-gp, also known as P-glycoprotein, Pg-170 or P-170, plays an important role in MDR. 

An aqueous extract of Tinospora cordifolia has been found to induce leucocytosis with predominant neutrophilia and blunt the leucopenic effects of cyclophosphamide (a cytotoxic drug used in cancer chemotherapy). These effects were comparable to those of lithium carbonate and glucan [23, 24]. 

Cancer is characterized by the uncontrolled growth of cells. Because cancer cells cannot multiply if they cannot synthesize DNA, scientists have searched for compounds that interfere with DNA synthesis. 5-Fluoruracil (yellow molecule), one of the oldest drugs used in cancer chemotherapy, is such a compound. We will see that it acts by binding to the enzyme (purple and green molecule), that catalyzes the synthesis of thymidine, an essential component of DNA. Once bound to the enzyme, 5-fluorouracil prevents an elimination reaction that is required for the continued synthesis of thymidine (Section 24.7). 

A number of drugs resemble normal body substances and thus may be transformed by rather specific enzymes. For example, most sympathomimetic amines resemble norepinephrine and thus are metabolized by enzymes which act on this neurotransmitter. Similarly, a number of drugs used in cancer chemotherapy... 

A rare case of enzyme catalyzing imine reduction reaction (see also Section 13.4.4) is the stereoselective reduction of dihydrofolic acid to (6S)-tetrahydrofolic acid by dihydrofolate reductase (DHFR) at the expense of NADPH. This biocatalytic step was employed in the synthesis of (S)-leucovorin [(6S)-5-formyl-5,6,7,8-tetrahydro-folate], a drug used in cancer chemotherapy. DHFR produced by E. coli was combined with a GDH/glucose cofactor recycling system and yielded (6S)-tetrahy-drofolic acid, which upon formylation furnished L-leucovorin with >99.5% de (Figure 13.31) [37-39]. 

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