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The progress of cancer chemotherapy has made a large contribution to the significant improvement of cure rate in patients with hematological malignancy including malignant lymphoma. Interpatient variability characterizes the disposition of many drugs. In the case of drugs with a wide therapeutic index, such variability is unlikely to affect either clinical efficacy or toxicity. With anticancer drugs, however, there is much less margin for error, due to their very narrow therapeutic index. Therefore, it is crucially important to understanding the mechanism of action, pharmacokinetics and pharmacodynamics of each anticancer drug in order to give chemotherapy in safety. Overview of the pharmacological functions of anticancer agent using in malignant lymphoma is the subject of this chapter.

Hyperuricemia reflects extracellular fluid supersaturation for uric acid. Although dietary, genetic, or disease-related excesses in urate production underlie hyperuricemia in some cases, impaired renal excretion of uric acid is the dominant cause of hyperuricemia. This type of hyperuricemia may be primary (idiopathic) and unassociated with an identifiable disorder. Two important candidates that may affect renal urate excretion were identified recently. One is an organic anion transporter (OAT) family member called urate transporter (URAT) 1. URAT1 has highly specific urate transport activity, exchanging this anion with others including most of the endogenous organic anions and drug anions that are known to affect renal uric acid transport. Another is uromodulin (UMOD), which is the key protein for the pathogenesis of familial juvenile hyperuricemic nephropathy that is characterized by early onset of hyperuricemia and renal failure. The role of these proteins in the cause of hyperuricemia is under investigation.

Gout is a type of inflammatory arthritis that is triggered by the crystallization of monosodium urate (MSU) within the joints and is often associated with hyperuricemia. Further understanding the physiology and dynamics of uric acid in human is required to make sure the disease mechanism of both gout and hyperuricemia in clinic. The amount of urate in the body consists urate pool, and which depends on the balance between dietary intake, synthesis, and excretion. Uric acid is a weak acid that exists largely as MSU, the ionized form, in urate pool at physiologic pH. But the solubility of MSU is influenced of pH, temperature and protein of blood and tissue.

Imatinib mesylate (imatinib), a selective inhibitor of BCR-ABL tyrosine kinase, has shown excellent efficacy in patients with chronic myelogenous leukemia (CML) in the chronic phase, however, it does not in those in the accelerated phase or blastic crisis. In patients with CML who have undergone allogeneic stem cell transplantation, imatinib has the capability to induce hematological and even molecular response, and provides a prolonged survival among those in the chronic and accelerated phases. It has been demonstrated that major cytogenic response is a surrogate marker for survival in cases receiving imatinib. It has also been demonstrated that a genome-wide cDNA microarray enables the prediction of sensitivity to imatinib. The acquired resistance in patients who failed to respond to imatinib seemed to be induced by several point mutations in the BCR-ABL gene, which were likely to affect the binding of imatinib with BCR-ABL. Polyclonal cells which harbor distinct mutations in a single patient seemed to be selected in vivo under the selective pressure of imatinib, indicating the rationale of combined treatment with other types of agents. Recently, SPIRIT (STI571 Prospective International Randomized Trials) have been conducted, in which the efficacy of imatinib monotherapy, and imatinib combined with interferon or cytarabine were compared. New agents which inhibit the signaling pathway related to BCR-ABL, such as adaphostin (NSC680410), farnesyltransferase inhibitor SCH66336, MAP kinase inhibitor PD184352, PD98059, U0126, and antibiotic geldanamycin, have shown excellent activity combined with imatinib in vitro.