Using Pharmacology to Squeeze the Life Out of Childhood Leukemia, and Potential Strategies to Achieve Breakthroughs in Medulloblastoma Treatment

The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia

“…MTX is a crucial therapeutic agent for the successful treatment of ALL [ 1 ]. Since its first clinical trial in 1953 using a mini-dosage, the overall prognosis of childhood ALL has ameliorated [ 1 ]. Higher MTX dose increases the cure rate of childhood ALL [ 17 ].…”

“…Increased potassium excretion due to rapid hydration may also be the cause of hypokalemia. MTX dose is another risk factor for nephrotoxicity [ 1 ]. In our research, the results suggested that patients with the TT genotype received a higher MTX dose.…”

“…Methotrexate (MTX) is a crucial agent in treating pediatric acute lymphoblastic leukemia (ALL). It interferes with folate metabolism [ 1 , 2 ]. Upon entering cells through the reduced folate carrier, MTX competitively inhibits dihydrofolate reductase, which leads to reduced conversion of dihydrofolate to tetrahydrofolate.…”

“…High-dose methotrexate (HD-MTX) chemotherapy is defined as MTX >500 mg/m 2 and is part of the regimen for pediatric ALL [ 1 , 2 ]. High-intensity chemotherapy can improve the overall prognosis of childhood ALL, but can also cause severe toxicities.…”

Cancer: slaying the nine-headed Hydra

“…Ultimately, however, data from cancers that are cured by therapy, such as pediatric leukemias, imply that all heads of the cancer hydra must be slayed from the outset. [61][62][63][64] Other important considerations may apply. The combination approach may result in higher response rates, not from either synergy or an additive effect but, when applied to a population without biomarker selection, from targeting different subgroups within that population, as shown by Palmer et al [65] The latter emphasizes the crucial importance of molecular profiling of each patient in order to limit the combination of drugs given to them to those that will impact their tumor, hence reducing toxicity from drugs that may only impact other subgroups of the population.…”