Despite most of the prolactinomas can be treated with endocrine therapy
and/or surgery, a significant percentage of these tumors can be
resistant to endocrine treatments and/or recur with prominent invasion
into the surrounding anatomical structures. Hence, clinical, pathological, and
molecular definitions of aggressive prolactinomas are important to guide for
classical and novel treatment modalities. In this review, we aimed to define
molecular endocrinological features of dopamine agonist-resistant and aggressive
prolactinomas for designing future multimodality treatments. Besides surgery,
temozolomide chemotherapy and radiotherapy, peptide receptor radionuclide
therapy, estrogen pathway modulators, progesterone antagonists or agonists,
mTOR/akt inhibitors, pasireotide, gefitinib/lapatinib,
everolimus, and metformin are tested in preclinical models, anecdotal cases, and
in small case series. Moreover, chorionic gonadotropin, gonadotropin releasing
hormone, TGFβ and PRDM2 may seem like possible future targets for
managing aggressive prolactinomas. Lastly, we discussed our management of a
unique prolactinoma case by asking which tumors’ proliferative index
(Ki67) increased from 5–6% to 26% in two subsequent
surgeries performed in a 2-year period, exerted massive invasive growth, and
secreted huge levels of prolactin leading up to levels of 1 605
671 ng/dl in blood.
Many investigations exist regarding the effect of the DNA repair enzyme MGMT (O6-methylguanine- DNA-methyltransferase)-encoding gene methylation on the antineoplasticity of temozolomide in glioblastoma patients. However, there exist surprisingly lesser studies regarding the associations between MGMT enzyme biochemistry with glial carcinogenesis. MGMT involves in risk of malignancies associated with ionizing radiation, smoking, exposure to polycyclic aromatic hydrocarbons, chlorinated solvents, vinylchloride and hairdyes. All these factors are also proposed to link with gliomagenesis, yet MGMT interactions with these carcinogens in gliomagenesis are not studied yet. In future, MGMT sequencing may be employed in vulnerable populations working in industries associated with exposure to these carcinogens to develop preventive strategies. Given that MGMT is involved in DNA repair, a polymorphism may simultaneously modify the risk of gliomas while enhancing temozolomide cytotoxicity in both marrow and tumor cells.
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