Beyond EGFR inhibition: multilateral combat strategies to stop the progression of head and neck cancer

변형권,구민희,양재문 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-

Epidermal growth factor receptor (EGFR) overexpression is common in head and neck squamous cell carcinoma. Targeted therapy specifically directed towards EGFR has been an area of keen interest in head and neck cancer research, as EGFR is potentially an integration point for convergent signaling. Despite the latest advancements in cancer diagnostics and therapeutics against EGFR, the survival rates of patients with advanced head and neck cancer remain disappointing due to anti-EGFR resistance. This review article will discuss recent multilateral efforts to discover and validate actionable strategies that involve signaling pathways in heterogenous head and neck cancer and to overcome anti-EGFR resistance in the era of precision medicine. Particularly, this review will discuss in detail the issue of cancer metabolism, which has recently emerged as a novel mechanism by which head and neck cancer may be successfully controlled according to different perspectives.

비강과 비인강에 발생한 Rosai-Dorfman 병 1예

변형권,김유석,최준성,윤주헌 대한이비인후과학회 2008 대한이비인후과학회지 두경부외과학 Vol.51 No.6

Rosai-Dorfman disease is a rare disorder of unknown etiology and is usually associated with benign proliferation of hematopoietic and fibrous tissue that often manifests in the head and neck region. The most common clinical presentation of this entity is bilateral, nontender cervical lymphadenopathy, but an extranodal form of the disease may develop in up to 43% of patients. We report a case of extranodal Rosai-Dorfman disease occurring in the nasal cavity and the nasopharynx. A 25-year-old male visited the clinic with a complaint of nasal obstruction for several months. Mass originating from anterior portion of septum and nasopharyngeal cavity was observed by endoscopy. Endoscopic guided incisional biopsy of the lesion was performed. The histopathologic findings revealed clusters of large, foamy histiocytes with abundant clear cytoplasm, lymphophagocytosis, and heavy infiltration of lymphocytes and plasma cells, which are the key features of Rosai-Dorfman disease. (Korean J Otorhinolaryngol- Head Neck Surg 2008;51:570-3)

두경부암의 표적 치료제 저항성 기전

변형권 대한이비인후과학회 2016 대한이비인후과학회지 두경부외과학 Vol.59 No.3

Head and neck squamous cell carcinoma has emerged as the sixth most commonly occurring cancer worldwide and despite advances in diagnostics and therapeutics, the treatment results and survival outcomes still remain poor, especially in advanced cancers. Due to the complexity of the local anatomic structures and the importance as vital functioning organs, the head and neck area following conventional treatment modalities such as surgery, chemotherapy, or radiotherapy often result as a devastating consequence both esthetically and functionally. In order to minimize the treatment related sequelae and at the same time maximize treatment effect, tumor-specific molecular targeted therapy has become an area under active research. Several molecular targeted agents, including the representative epidermal growth factor receptor (EGFR)-inhibitors have been developed and its therapeutic effects investigated. However, therapeutic resistance has newly risen as a main problem following targeted therapy due to a variety of resistance mechanisms. This review article looks at the major acquired resistance mechanisms following targeted agents administration including EGFR inhibitors and many others and strategies to overcome the resistance to achieve precision medicine. Korean J Otorhinolaryngol-Head Neck Surg 2016;59(3):181-7

BRAF(V600E) 돌연변이 갑상선 역형성암에서 BRAF(V600E) 억제에 의한 EGFR 발현 증가가 표적치료에 대한 저항성발현과 상피-간질세포이행과정에 미치는 영향분석

변형권(Hyung Kwon Byeon),나휘정(Hwi Jung Na),양연주(Yeon Ju Yang),박재홍(Jae Hong Park),권형주(Hyeong Ju Kwon),장재원(Jae Won Chang),반명진(Myung Jin Ban),김원식(Won Shik Kim),신동엽(Dong Yeob Shin),이은직(Eun Jig Lee),고윤우(Yoon Wo 대한두경부종양학회 2014 대한두경부 종양학회지 Vol.30 No.2

Background and Objectives:Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid ma-lignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods:Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same ex-periment was performed on both orthotopic and ectopic xenograft mouse models. Results:FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion:EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

중두개와 접근법을 이용하여 재수술로 안면신경 및 청력 기능보존을 시행한 청신경종양1예

양원선,변형권,강재정,이원상 대한이비인후과학회 2008 대한이비인후과학회지 두경부외과학 Vol.51 No.2

The aim of surgery for vestibular schwannoma is to accomplish complete tumor removal while preserving facial function and hearing ability. The middle cranial fossa approach represents one such surgical approach for resection of vestibular schwannoma with hearing preservation. As more experience has been gained with this approach, hearing preservation rates have increased. However, even if gross tumor removal is done completely, residual tumor can show regrowth microscopically. Such residual vestibular schwannoma may be treated by different options. We present a case of residual vestibular schwannoma treated with revision middle cranial fossa approach to preserve facial function and hearing ability. (Korean J Otorhinolaryngol-Head Neck Surg 2008;51:174-7)

구인두암 환자에서 술후 동시화학방사선요법을 시행한 후 발생한 다발성 인두피부누공 1예

오현석,전경화,변형권 대한이비인후과학회 2021 대한이비인후과학회지 두경부외과학 Vol.64 No.8

Pharyngocutaneous fistula is a readily encountered complication that occurs after surgery forlaryngopharyngeal cancer. The development of pharyngocutaneous fistula increases hospitalization,delays postoperative adjuvant treatment, and can lead to serious complications such aswound infection and carotid artery rupture. Transoral robotic surgery (TORS) is actively beingperformed as a standard procedure for surgery of pharyngeal and laryngeal cancers. Manyreports verified that TORS is advantageous in terms of perioperative outcomes such as decreasedhospitalization and reduced rate of postoperative complications, free flap reconstruction,and tracheostomy or gastrostomy tube dependence relative to open surgery. However,careful selection of patients is mandatory and there are some critical points to consider in optimaltreatment outcomes. Recently, we experienced a 47-year-old patient with tonsillar cancerwho underwent lateral oropharyngectomy by TORS and radical neck dissection. Unfortunately,multiple pharyngocutaneous fistulae occurred following postoperative concurrent chemoradiotherapy(CCRT). Multiple phrayngocutaneous fistulae following TORS and postoperativeCCRT have not been reported in the literature. Therefore, we report this case with a briefdiscussion supported by a review of the relevant literature.

Anterolateral Thigh Thickness Measurement in Positron Emission Tomography-Computed Tomography for the Prediction of Free Flap Reconstruction Outcomes in Head and Neck Cancer

반명진,박재홍,변형권,장재원,안정현,김지훈,김원식,고윤우,김세헌,최은창 대한이비인후과학회 2016 대한이비인후과학회지 두경부외과학 Vol.59 No.11

Background and Objectives Anterolateral thigh (ALT) flaps are commonly used for head and neck surgery reconstruction. However, a thick ALT often leads to long operation times. Therefore, ALT thickness on a preoperative non contrast image of positron emission tomography-computed tomography (PET-CT) scan was measured to predict surgical outcome. Subjects and Method The correlation between ALT thickness and total reconstruction time was analyzed in 106 patients. The differences in ALT thickness between the successful and compromised-flap groups were analyzed retrospectively. Results Median ALT thickness was 4.49 mm, and total reconstruction time was 190 min. Total reconstruction time was significantly correlated with ALT thickness (p=0.019). ALT thickness, body mass index (BMI), total reconstruction time and ischemia time were significantly greater in the compromised-flap group than in the successful group. In the multivariate analysis, only BMI and ischemia time were predictors for the compromised flap. Conclusion ALT thickness measured on a non-contrast image of PET-CT scan is useful as a surgical outcome predictor with respect to total reconstruction time. A further study may suggest the risk of a thick ALT in a compromised flap in head and neck reconstruction using an ALT free flap. Korean J Otorhinolaryngol-Head Neck Surg 2016;59(11):780-6

두경부암의 지방산 대사 표적화

김지훈,구민희,양재문,변형권 대한이비인후과학회 2021 대한이비인후과학회지 두경부외과학 Vol.64 No.6

Reprogramming of cellular metabolism is an important, emerging, and universal hallmark ofcancer which has received considerable attention during the recent era of cancer research. Cancer cells show characteristic alterations in glucose metabolism in order to fulfill the needsof biosynthesis for tumor proliferation and growth. However, under certain circumstancessuch as invasion and metastasis, cancer cells are prone to metabolic stress and will requiredifferent strategies to meet the high energetic demand from cancer progression. From variousmetabolic rewiring mechanisms, cancer cells adopt other metabolic pathways with alternativenutrient sources. Therefore, targeting cancer metabolism holds promising but great challengecaused by the metabolic plasticity of cancer cells. This review will discuss characteristic cancermetabolism in detail with special focus on lipid metabolism which is gathering increasinglykeen interest, in order to find novel therapeutic approaches to head and neck cancer. By understandingand exploiting the synthesis, oxidation, and storage of fatty acids, we couldinvestigate potential strategies to block cancer proliferation and progression

성대폴립 환자에서 수술 후 음성치료의 유효성

오동주,김소연,최인학,한혜민,변형권,정광윤,백승국 대한이비인후과학회 2018 대한이비인후과학회지 두경부외과학 Vol.61 No.12

Background and Objectives Previous studies have suggested the usefulness and importanceof postoperative voice therapy, for which there are indirect and direct methods. The aimof this study was to evaluate the efficacy of treatment according to different voice therapymethods. Subjects and Method Patients with vocal polyp were divided into three groups. Group 1 receiveddirect voice therapy after phonomicrosurgery and Group 2 indirect voice therapy afterphonomicrosurgery. Group 3 did not receive any voice therapy. Results Perceptual, acoustic, aerodynamic voice outcome parameters differed significantlybetween pre and post-operative treatments. In almost all of the voice analysis, Group 1, whounderwent direct voice therapy, improved more significantly compared with Group 2 and 3. Conclusion Postoperative voice therapy following phonomicrosurgery may be an effectiveadjuvant treatment in patients with vocal polyps. In particular, direct voice therapy can be effectivefor improving postoperative voice outcome.

음성 활동 및 참여 프로파일-한국판(K-VAPP): 타당성 검증 연구

이승진,최홍식,김향희,변형권,임성은,양민교 한국언어청각임상학회 2016 Communication Sciences and Disorders Vol.21 No.4

배경 및 목적: 우리나라 음성 클리닉의 임상 현장에서는 환자 보고에 의한 심리측정적 평가도구가 부족하며, 활동 및 참여 측면까지 고려한 검사도구는 전무하다. 이에, 본 연구에서는 ‘음성 활동 및 참여 프로파일-한국판(K-VAPP)’의 타당성을 검증하고자 하였다. 방법: 개념적 및 언어적 등가성을 위해 권고되는 절차에 따라 ‘음성 활동 및 참여 프로파일’을 한국어로 번역하여 300명의 대상자(음성장애 환자 150명 및 대조군 150명)에게 시행하였다. 타당도 검증을 위해 5년 이상 경력의 언어재활사 4인의 검증과 예비시행, 집단 간 점수 비교, 문항변별도 산출과 음성장애지수와의 상관관계 검증을 실시하였다. 신뢰도 검증을 위해 내적 일치도, 검사-재검사 신뢰도를 산출하고, 절단점을 확인하였다. 결과: 환자군의 총점, 활동 제한 점수, 참여 제약 점수, 하위영역별 점수가 대조군에 비해 높았으며, 충분한 수준의 신뢰도 및 타당도를 갖춘 검사도구임이 확인되었다. 총점, 활동 제한 점수, 참여 제약 점수의 절단점은 각각 14.5점, 4.5점, 1.5점이었다. 논의 및 결론: K-VAPP가 우리나라 음성장애 임상현장에서 충분한 타당도와 신뢰도를 갖춘 도구로 활용될 수 있음을 확인하였다.