Hypertriglyceridemia: An Open Door for Cancer Treatment?

Does lipid management have a significant role in cancer treatment? Could hypertriglyceridemia be an accelerating factor in certain tumors? These questions have grown from the long-standing recognition of the relationship of lipids to certain cancers. Cancers express high levels of lipid synthase, the enzyme responsible for the production of fatty acids. Lymphoma and other cancers have been found to have the ability to generate the lipids via de novo lipogenesis at a rate faster than other lipogenetic tissues [1]. Continuous de novo lipogenesis provides cancer cells with membrane building blocks, signaling lipid molecules, posttranslational modifications of proteins as well as energy supply to support rapid cell proliferation [2]. Protection of cancer cells by apoptosis by overexpression of fatty acid synthase (FASN) also helps the progression of the cancer [2]. Recent studies have documented the changes in lipid levels in the etiology and most importantly prognosis of cancer [3, 4]. There are many studies that have shown that the degree of lipid abnormality was directly related to the underlying tumor burden in addition to the abnormality in triglyceride clearance [5]. In one study, 25 patients with acute leukemia and nonHodgkin’s lymphoma (NHL) were studied; all patients demonstrated an abnormality in at least one plasma lipid fraction that consisted of extremely low levels of high density lipoprotein (HDL), elevated triglycerides (TG) and elevated very low density lipoprotein (VLDL). The levels were found to be normalized after recovery [5]. Another study was performed to investigate serum lipid alterations in patients with acute lymphoblastic leukemia (ALL) at diagnosis and during remission of the disease. Plasma lipids and lipoproteins were measured at diagnosis, prior to the administration of induction treatment, and every 2 months for the first 12 months of the maintenance phase of chemotherapy in 64 patients with ALL. Nearly all patients demonstrated serum lipid alterations which included elevated TG, LDL and cholesterol and values were returned back to normal during remission [6]. This points out the direct link between cancer progression and lipid levels. Metastasis is another interesting area in which the lipid level can correlate with disease burden. In one study, 205 Iranian patients from Semnan Oncology Clinic were studied and there was a significant association between higher levels of serum LDL and metastasis [7]. Aggressiveness of the tumor including metastasis can be highlighted by the levels of lipids. This brings up to the point of our case. We present a patient with stage IV diffuse large B-cell NHL with diffuse involvement of the bone and liver whose course was complicated with an incidental finding of hypertriglyceridemia. A 67-year-old Caucasian male with a past medical history of chronic obstructive pulmonary disease, diabetes mellitus, hypertension, coronary artery disease, and pulmonary embolism was admitted to the hospital for severe lower back pain and significant weight loss for 1 month. He denied any familial or personal history of hypertriglyceridemia. Physical examination was remarkable for pale conjunctivae, positive straight leg test on the left lower extremity, and a limited range of motion in his right upper extremity. There was no point tenderness noted in his back but there was mild tenderness to palpation of the right chest wall. CT abdomen imaging revealed several masses in the liver which involved the lateral segment of the left lobe, the medial segment, and an illdefined mass in the right lobe posteriorly. Biopsy of the liver demonstrated evidence for diffuse large B-cell NHL and bone marrow involvement was also seen in bone marrow biopsy. Lipid profile drawn 2 years ago were found to be TG 195 mg/ dL, cholesterol 146 mg/dL, LDL 74 mg/dL, VLDL 39 mg/dL and HDL 33 mg/dL. The lipid panel had changed dramatically during this admission demonstrating TG 1,154 mg/dL, cholesterol 204 mg/dL, and HDL 4 mg/dL, and LDL and VLDL were unable to be calculated. This unusual level of TG highlighted the aggressiveness of the tumor and more importantly the prognosis of the cancer. The patient was treated with gemfibrozil and insulin. TG levels were markedly improved from 1,154 to 690 mg/dL. The patient deteriorated before initiation of chemotherapy and expired. The issue of interest in this case is not the specific attributes of the cancer discussed but of the rise and fall of TG associated with it. The possible implications of this event may correlate with the aggressiveness of the tumor or the type of cancer and presents an intriguing possibility of manipulating this process as a means of treatment. The current standards for Manuscript accepted for publication March 24, 2016

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