NF1型恶性外周神经鞘瘤的研究进展
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摘要
恶性外周神经鞘瘤(MPNSTs)是临床上罕见的神经源性恶性肿瘤,约半数继发于1型神经纤维瘤病(NF1)。大多数NF1型MPNSTs高度恶性,有较高的局部复发率和远处转移率。截至目前,广泛切除术仍为局部MPNSTs的首选治疗方法。NF1型MPNSTs由于发生率低,治疗手段有限,预后较差,所以尚未受到广大医师的重视。近年来随着现代医疗科技的不断进步,NF1型MPNSTs的发病机制、诊断标准、治疗方案有了新的进展。已有多种新药物或方案被批准用于临床前或临床治疗使用,并取得了良好的效果。未来,随着对NF1型MPNSTs生物学特性认识的不断加深,其治愈将成为可能。
Malignant peripheral nerve sheath tumors( MPNSTs) are clinically rare neurogenic malignancies,and about half of MPNSTs are secondary to neurofibromatosis type 1( NF1). Most of MPNSTs with NF1 are highly malignant with higher rates of local recurrences and distant metastases. To date,extensive resection is still the preferred treatment for local MPNSTs. Due to the low incidences,limited treatments and poorer prognoses of MPNSTs with NF1,they have not received enough attention from most doctors. With the continuous advancement of modern medical technology in recent years,there have been new advances in pathogeneses,diagnostic criteria,and treatments of MPNSTs with NF1. A variety of new drugs and protocols have been approved for preclinical and clinical therapies with good treatment effects. In the future,with the increasing understanding of the biological characteristics of MPNSTs with NF1,the cure will become possible.
Malignant peripheral nerve sheath tumors( MPNSTs) are clinically rare neurogenic malignancies,and about half of MPNSTs are secondary to neurofibromatosis type 1( NF1). Most of MPNSTs with NF1 are highly malignant with higher rates of local recurrences and distant metastases. To date,extensive resection is still the preferred treatment for local MPNSTs. Due to the low incidences,limited treatments and poorer prognoses of MPNSTs with NF1,they have not received enough attention from most doctors. With the continuous advancement of modern medical technology in recent years,there have been new advances in pathogeneses,diagnostic criteria,and treatments of MPNSTs with NF1. A variety of new drugs and protocols have been approved for preclinical and clinical therapies with good treatment effects. In the future,with the increasing understanding of the biological characteristics of MPNSTs with NF1,the cure will become possible.
引文
[1]王玉洁,王彦晖,奚胜艳,等.癌症“种子土壤说”新论[J].中华中医药杂志,2018,33(3):975-979.
[2] Farid M,Demicco EG,Garcia R,et al. Malignant peripheral nerve sheath tumors[J]. Oncologist,2014,19(2):193-201.
[3] CarrióM,Gel B,Terribas E,et al. Analysis of intratumor heterogeneity in neurofibromatosis type 1 plexiform neurofibromas and neurofibromas with atypical features:Correlating histological and genomic findings[J]. Hum Mutat,2018,39(8):1112-1125.
[4] Nguyen R,Jett K,Harris GJ,et al. Benign whole body tumor volume is a risk factor for malignant peripheral nerve sheath tumors in neurofibromatosis type 1[J]. J Neurooncol,2014,116(2):307-313.
[5] Wasa J,Nishida Y,Tsukushi S,et al. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas[J]. AJR Am J Roentgenol,2010,194(6):1568-1574.
[6] Ahlawat S,Blakeley J,Montgomery E,et al. Schwannoma in neurofibromatosis type 1:A pitfall for detecting malignancy by metabolic imaging[J]. Skeletal Radiol,2013,42(9):1317-1322.
[7] Meany H,Dombi E,Reynolds J,et al. 18-fluorodeoxyglucosepositron emission tomography(FDG-PET)evaluation of nodular lesions in patients with neurofibromatosis type 1 and plexiform neurofibromas(PN)or malignant peripheral nerve sheath tumors(MPNST)[J]. Pediatr Blood Cancer,2013,60(1):59-64.
[8] Bernthal NM,Putnam A,Jones KB,et al. The effect of surgical margins on outcomes for low grade MPNSTs and atypical neurofibroma[J]. J Surg Oncol,2014,110(7):813-816.
[9] Shuayb M,Begum R. Unusual primary breast cancer-malignant peripheral nerve sheath tumor:A case report and review of the literature[J]. J Med Case Rep,2017,11(1):161.
[10] Uusitalo E,Rantanen M,KallionpRA,et al. Distinctive cancer associations in patients with neurofibromatosis type 1[J]. J Clin Oncol,2016,34(17):1978-1986.
[11] Rodriguez FJ,Folpe AL,Giannini C,et al. Pathology of peripheral nerve sheath tumors:Diagnostic overview and update on selected diagnostic problems[J]. Acta Neuropathol,2012,123(3):295-319.
[12] Ducatman BS,Scheithauer BW,Piepgras DG,et al. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120cases[J]. Cancer,1986,57(10):2006-2021.
[13] Zou C,Smith KD,Liu J,et al. Clinical,pathological,and molecular variables predictive of malignant peripheral nerve sheath tumor outcome[J]. Ann Surg,2009,249(6):1014-1022.
[14] Kolberg M,Hland M,Agesen TH,et al. Survival meta-analyses for> 1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1[J]. Neuro Oncol,2013,15(2):135-147.
[15] Widemann BC. Current status of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors[J].Curr Oncol Rep,2009,11(4):322-328.
[16] Lee W,Teckie S,Wiesner T,et al. PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors[J]. Nat Genet,2014,46(11):1227-1232.
[17] Staedtke V,Bai RY,Blakeley JO. Cancer of the peripheral nerve in neurofibromatosis type 1[J]. Neurotherapeutics,2017,14(2):298-306.
[18] Birindelli S,Perrone F,Oggionni M,et al. Rb and TP53 pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumors[J]. Lab Invest,2001,81(6):833-844.
[19] Carroll SL. The challenge of cancer genomics in rare nervous system neoplasms:Malignant peripheral nerve sheath tumors as a paradigm for cross-species comparative oncogenomics[J]. Am J Pathol,2016,186(3):464-477.
[20] Kourea HP,Orlow I,Scheithauer BW,et al. Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas[J]. Am J Pathol,1999,155(6):1855-1860.
[21] Keng VW,Rahrmann EP,Watson AL,et al. PTEN and NF1 inactivation in Schwann cells produces a severe phenotype in the peripheral nervous system that promotes the development and malignant progression of peripheral nerve sheath tumors[J]. Cancer Res,2012,72(13):3405-3413.
[22] Schaefer IM,Fletcher CD,Hornick JL. Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics[J]. Mod Pathol,2016,29(1):4-13.
[23] Baude A,Lindroth AM,Plass C. PRC2 loss amplifies Ras signaling in cancer[J]. Nat Genet,2014,46(11):1154-1155.
[24] Lin L,Hutzen B,Zuo M,et al. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells[J]. Cancer Res,2010,70(6):2445-2454.
[25] Wu J,Patmore DM,Jousma E,et al. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors[J].Oncogene,2014,33(2):173-180.
[26] Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference[J]. Arch Neurol,1988,45(5):575-578.
[27] Karamchandani JR,Nielsen TO,van de Rijn M,et al. Sox10 and S100 in the diagnosis of soft-tissue neoplasms[J]. Appl Immunohistochem Mol Morphol,2012,20(5):445-450.
[28] Otsuka H,Kohashi K,Yoshimoto M,et al. Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors[J]. Pathol Res Pract,2018,214(3):417-425.
[29] Valentin T,Le Cesne A,Ray-Coquard I,et al. Management and prognosis of malignant peripheral nerve sheath tumors:The experience of the French Sarcoma Group(GSF-GETO)[J]. Eur J Cancer,2016,56:77-84.
[30] Carli M,Ferrari A,Mattke A,et al. Pediatric malignant peripheral nerve sheath tumor:The Italian and German soft tissue sarcoma cooperative group[J]. J Clin Oncol,2005,23(33):8422-8430.
[31] Kar M,Deo SV,Shukla NK,et al. Malignant peripheral nerve sheath tumors(MPNST)—clinicopathological study and treatment outcome of twenty-four cases[J]. World J Surg Oncol,2006,4:55.
[32] Kahn J,Gillespie A,Tsokos M,et al. Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors[J]. Front Oncol,2014,4:324.
[33] Clark MA,Fisher C,Judson I,et al. Soft-tissue sarcomas in adults[J]. N Engl J Med,2005,353(7):701-711.
[34] Pervaiz N,Colterjohn N,Farrokhyar F,et al. A systematic metaanalysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma[J]. Cancer,2008,113(3):573-581.
[35] Zehou O,Fabre E,Zelek L,et al. Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis1:A 10-year institutional review[J]. Orphanet J Rare Dis,2013,8:127.
[36] Barkan B,Starinsky S,Friedman E,et al. The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for neurofibromatosis type 1[J]. Clin Cancer Res,2006,12(18):5533-5542.
[37] Widemann BC,Dombi E,Gillespie A,et al. Phase 2 randomized,flexible crossover,double-blinded,placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas[J]. Neuro Oncol,2014,16(5):707-718.
[38] Johansson G,Mahller YY,Collins MH,et al. Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors[J]. Mol Cancer Ther,2008,7(5):1237-1245.
[39] Watson AL,Anderson LK,Greeley AD,et al. Co-targeting the MAPK and PI3K/AKT/m TOR pathways in two genetically engineered mouse models of schwann cell tumors reduces tumor grade and multiplicity[J]. Oncotarget,2014,5(6):1502-1514.
[40] Fujisawa T,Joshi BH,Puri RK. IL-13 regulates cancer invasion and metastasis through IL-13Ralpha2 via ERK/AP-1 pathway in mouse model of human ovarian cancer[J]. Int J Cancer,2012,131(2):344-356.
[41] Hsi LC,Kundu S,Palomo J,et al. Silencing IL-13Ralpha2promotes glioblastoma cell death via endogenous signaling[J].Mol Cancer Ther,2011,10(7):1149-1160.
[42] Madhankumar AB,Mrowczynski OD,Slagle-Webb B,et al. Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors[J]. PLo S One,2018,13(1):e181529.
[43] Dingli D,Peng KW,Harvey ME,et al. Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter[J]. Blood,2004,103(5):1641-1646.
[44] Russell SJ,Federspiel MJ,Peng KW,et al. Remission of disseminated cancer after systemic oncolytic virotherapy[J]. Mayo Clin Proc,2014,89(7):926-933.
[45] Deyle DR,Escobar DZ,Peng KW,et al. Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors[J]. Gene,2015,565(1):140-145.
[46] Sweeney EE,Burga RA,Li C,et al. Photothermal therapy improves the efficacy of a MEK inhibitor in neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors[J]. Sci Rep,2016,6:37035.
[2] Farid M,Demicco EG,Garcia R,et al. Malignant peripheral nerve sheath tumors[J]. Oncologist,2014,19(2):193-201.
[3] CarrióM,Gel B,Terribas E,et al. Analysis of intratumor heterogeneity in neurofibromatosis type 1 plexiform neurofibromas and neurofibromas with atypical features:Correlating histological and genomic findings[J]. Hum Mutat,2018,39(8):1112-1125.
[4] Nguyen R,Jett K,Harris GJ,et al. Benign whole body tumor volume is a risk factor for malignant peripheral nerve sheath tumors in neurofibromatosis type 1[J]. J Neurooncol,2014,116(2):307-313.
[5] Wasa J,Nishida Y,Tsukushi S,et al. MRI features in the differentiation of malignant peripheral nerve sheath tumors and neurofibromas[J]. AJR Am J Roentgenol,2010,194(6):1568-1574.
[6] Ahlawat S,Blakeley J,Montgomery E,et al. Schwannoma in neurofibromatosis type 1:A pitfall for detecting malignancy by metabolic imaging[J]. Skeletal Radiol,2013,42(9):1317-1322.
[7] Meany H,Dombi E,Reynolds J,et al. 18-fluorodeoxyglucosepositron emission tomography(FDG-PET)evaluation of nodular lesions in patients with neurofibromatosis type 1 and plexiform neurofibromas(PN)or malignant peripheral nerve sheath tumors(MPNST)[J]. Pediatr Blood Cancer,2013,60(1):59-64.
[8] Bernthal NM,Putnam A,Jones KB,et al. The effect of surgical margins on outcomes for low grade MPNSTs and atypical neurofibroma[J]. J Surg Oncol,2014,110(7):813-816.
[9] Shuayb M,Begum R. Unusual primary breast cancer-malignant peripheral nerve sheath tumor:A case report and review of the literature[J]. J Med Case Rep,2017,11(1):161.
[10] Uusitalo E,Rantanen M,KallionpRA,et al. Distinctive cancer associations in patients with neurofibromatosis type 1[J]. J Clin Oncol,2016,34(17):1978-1986.
[11] Rodriguez FJ,Folpe AL,Giannini C,et al. Pathology of peripheral nerve sheath tumors:Diagnostic overview and update on selected diagnostic problems[J]. Acta Neuropathol,2012,123(3):295-319.
[12] Ducatman BS,Scheithauer BW,Piepgras DG,et al. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120cases[J]. Cancer,1986,57(10):2006-2021.
[13] Zou C,Smith KD,Liu J,et al. Clinical,pathological,and molecular variables predictive of malignant peripheral nerve sheath tumor outcome[J]. Ann Surg,2009,249(6):1014-1022.
[14] Kolberg M,Hland M,Agesen TH,et al. Survival meta-analyses for> 1800 malignant peripheral nerve sheath tumor patients with and without neurofibromatosis type 1[J]. Neuro Oncol,2013,15(2):135-147.
[15] Widemann BC. Current status of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors[J].Curr Oncol Rep,2009,11(4):322-328.
[16] Lee W,Teckie S,Wiesner T,et al. PRC2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors[J]. Nat Genet,2014,46(11):1227-1232.
[17] Staedtke V,Bai RY,Blakeley JO. Cancer of the peripheral nerve in neurofibromatosis type 1[J]. Neurotherapeutics,2017,14(2):298-306.
[18] Birindelli S,Perrone F,Oggionni M,et al. Rb and TP53 pathway alterations in sporadic and NF1-related malignant peripheral nerve sheath tumors[J]. Lab Invest,2001,81(6):833-844.
[19] Carroll SL. The challenge of cancer genomics in rare nervous system neoplasms:Malignant peripheral nerve sheath tumors as a paradigm for cross-species comparative oncogenomics[J]. Am J Pathol,2016,186(3):464-477.
[20] Kourea HP,Orlow I,Scheithauer BW,et al. Deletions of the INK4A gene occur in malignant peripheral nerve sheath tumors but not in neurofibromas[J]. Am J Pathol,1999,155(6):1855-1860.
[21] Keng VW,Rahrmann EP,Watson AL,et al. PTEN and NF1 inactivation in Schwann cells produces a severe phenotype in the peripheral nervous system that promotes the development and malignant progression of peripheral nerve sheath tumors[J]. Cancer Res,2012,72(13):3405-3413.
[22] Schaefer IM,Fletcher CD,Hornick JL. Loss of H3K27 trimethylation distinguishes malignant peripheral nerve sheath tumors from histologic mimics[J]. Mod Pathol,2016,29(1):4-13.
[23] Baude A,Lindroth AM,Plass C. PRC2 loss amplifies Ras signaling in cancer[J]. Nat Genet,2014,46(11):1154-1155.
[24] Lin L,Hutzen B,Zuo M,et al. Novel STAT3 phosphorylation inhibitors exhibit potent growth-suppressive activity in pancreatic and breast cancer cells[J]. Cancer Res,2010,70(6):2445-2454.
[25] Wu J,Patmore DM,Jousma E,et al. EGFR-STAT3 signaling promotes formation of malignant peripheral nerve sheath tumors[J].Oncogene,2014,33(2):173-180.
[26] Neurofibromatosis. Conference statement. National Institutes of Health Consensus Development Conference[J]. Arch Neurol,1988,45(5):575-578.
[27] Karamchandani JR,Nielsen TO,van de Rijn M,et al. Sox10 and S100 in the diagnosis of soft-tissue neoplasms[J]. Appl Immunohistochem Mol Morphol,2012,20(5):445-450.
[28] Otsuka H,Kohashi K,Yoshimoto M,et al. Immunohistochemical evaluation of H3K27 trimethylation in malignant peripheral nerve sheath tumors[J]. Pathol Res Pract,2018,214(3):417-425.
[29] Valentin T,Le Cesne A,Ray-Coquard I,et al. Management and prognosis of malignant peripheral nerve sheath tumors:The experience of the French Sarcoma Group(GSF-GETO)[J]. Eur J Cancer,2016,56:77-84.
[30] Carli M,Ferrari A,Mattke A,et al. Pediatric malignant peripheral nerve sheath tumor:The Italian and German soft tissue sarcoma cooperative group[J]. J Clin Oncol,2005,23(33):8422-8430.
[31] Kar M,Deo SV,Shukla NK,et al. Malignant peripheral nerve sheath tumors(MPNST)—clinicopathological study and treatment outcome of twenty-four cases[J]. World J Surg Oncol,2006,4:55.
[32] Kahn J,Gillespie A,Tsokos M,et al. Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors[J]. Front Oncol,2014,4:324.
[33] Clark MA,Fisher C,Judson I,et al. Soft-tissue sarcomas in adults[J]. N Engl J Med,2005,353(7):701-711.
[34] Pervaiz N,Colterjohn N,Farrokhyar F,et al. A systematic metaanalysis of randomized controlled trials of adjuvant chemotherapy for localized resectable soft-tissue sarcoma[J]. Cancer,2008,113(3):573-581.
[35] Zehou O,Fabre E,Zelek L,et al. Chemotherapy for the treatment of malignant peripheral nerve sheath tumors in neurofibromatosis1:A 10-year institutional review[J]. Orphanet J Rare Dis,2013,8:127.
[36] Barkan B,Starinsky S,Friedman E,et al. The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for neurofibromatosis type 1[J]. Clin Cancer Res,2006,12(18):5533-5542.
[37] Widemann BC,Dombi E,Gillespie A,et al. Phase 2 randomized,flexible crossover,double-blinded,placebo-controlled trial of the farnesyltransferase inhibitor tipifarnib in children and young adults with neurofibromatosis type 1 and progressive plexiform neurofibromas[J]. Neuro Oncol,2014,16(5):707-718.
[38] Johansson G,Mahller YY,Collins MH,et al. Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors[J]. Mol Cancer Ther,2008,7(5):1237-1245.
[39] Watson AL,Anderson LK,Greeley AD,et al. Co-targeting the MAPK and PI3K/AKT/m TOR pathways in two genetically engineered mouse models of schwann cell tumors reduces tumor grade and multiplicity[J]. Oncotarget,2014,5(6):1502-1514.
[40] Fujisawa T,Joshi BH,Puri RK. IL-13 regulates cancer invasion and metastasis through IL-13Ralpha2 via ERK/AP-1 pathway in mouse model of human ovarian cancer[J]. Int J Cancer,2012,131(2):344-356.
[41] Hsi LC,Kundu S,Palomo J,et al. Silencing IL-13Ralpha2promotes glioblastoma cell death via endogenous signaling[J].Mol Cancer Ther,2011,10(7):1149-1160.
[42] Madhankumar AB,Mrowczynski OD,Slagle-Webb B,et al. Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors[J]. PLo S One,2018,13(1):e181529.
[43] Dingli D,Peng KW,Harvey ME,et al. Image-guided radiovirotherapy for multiple myeloma using a recombinant measles virus expressing the thyroidal sodium iodide symporter[J]. Blood,2004,103(5):1641-1646.
[44] Russell SJ,Federspiel MJ,Peng KW,et al. Remission of disseminated cancer after systemic oncolytic virotherapy[J]. Mayo Clin Proc,2014,89(7):926-933.
[45] Deyle DR,Escobar DZ,Peng KW,et al. Oncolytic measles virus as a novel therapy for malignant peripheral nerve sheath tumors[J]. Gene,2015,565(1):140-145.
[46] Sweeney EE,Burga RA,Li C,et al. Photothermal therapy improves the efficacy of a MEK inhibitor in neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors[J]. Sci Rep,2016,6:37035.