Unmet Needs

최근 screening된 논문 80편이 시사하는 unmet needs를 위키 내부 근거로 정리했습니다.

개요

본 분석은 2026년 7월부터 9월까지 발표된 80편의 최신 문헌([1]-[80])을 근거로 합니다. 이 논문들은 주로 비소세포폐암(NSCLC), 소세포폐암(SCLC), 유방암, 간세포암(HCC) 및 기타 고형암과 혈액암에서의 정밀의학 접근법, 면역항암제 내성 기전, 그리고 인공지능(AI) 기반 영상 진단의 임상적 적용을 다룹니다. 전반적으로, 기존 표준 치료(표적치료, 화학요법, 단일 면역요법)의 한계를 극복하기 위해 종양 미세환경(TME)의 복잡한 상호작용을 표적으로 하는 새로운 전략과, AI를 활용한 비침습적 바이오마커 개발이 핵심 화두로 부상하고 있음을 시사합니다.

주요 unmet needs

1. 면역항암제(Immunotherapy) 내성 및 저항성 기전의 규명과 극복 전략 부족 다양한 고형암에서 anti-PD-1/PD-L1 요법에 대한 원발성 또는 획득성 내성이 여전히 주요 임상적 장벽으로 지적됩니다. NSCLC에서는 PD-L1의 비전통적 역신호 전달을 통한 대사 재프로그래밍([13]), HIF1A+CSF3R+ neutrophils에 의한 hypoxic niche 형성([7]), PGE2 매개 NK cell 기능 억제([40]), 그리고 IL20RB/JAK2/STAT3 경로 활성화([26]) 등이 내성 기전으로 규명되었습니다. 위암에서는 PRKX 매개 PD-L1 안정화([4])와 TGF-β1 유도 NETs 형성에 의한 CD8+ T cell exhaustion([44])이 문제가 됩니다. 또한, TNBC에서는 methylglyoxal stress에 의한 g-MDSC 확장([64])과 유방암/대장암에서 종양 미세환경 세포의 N-glycan이 CAR-T cell 기능을 억제하는 현상([67])이 보고되었습니다. 이러한 복잡한 면역 회피 기전을 표적으로 하는 새로운 약물(예: CXCR2 inhibitor, AARS1 inhibitor, MGAT5 inhibitor) 또는 병용 요법 전략에 대한 전향적 검증이 시급합니다.

2. 종양 이질성(Tumor Heterogeneity) 및 미세환경(TME) 공간 구조에 기반한 정밀 환자 분류의 부재 종양의 분자적·공간적 이질성이 치료 반응과 예후에 미치는 영향은 명확하나, 이를 임상적으로 통합하여 활용하는 표준화된 방법이 부족합니다. NSCLC에서 Fusion isoform multiplicity가 ALK-TKI 반응에 부정적 영향을 미친다는 점([59]), EGFR exon 19 deletion 하위 유형별 예후 차이([27]), 그리고 Tertiary lymphoid structures (TLS)의 spatial architecture(내부 vs 외부)가 HCC 예후에 상반된 영향을 준다는 발견([80])은 단순한 biomarker 존재 여부 이상의 정밀한 분류가 필요함을 시사합니다. 또한, SCLC에서 염증성(Inflamed) 하위 유형과 NEUROD1-driven 하위 유형의 치료 반응 차이([51]), 그리고 LS-SCLC에서 신보조 면역화학요법(NIC) 후 pCR 달성 환자의 'immune-hot' 표현형([66])은 환자 군집을 더 세분화하여 맞춤형 치료를 설계해야 할 필요성을 강조합니다.

3. 비침습적 영상 바이오마커 및 AI 기반 진단/예측 모델의 임상 표준화 및 검증 격차 AI와 Radiomics 기술이 종양 이질성 정량화([76]), EGFR 돌연변이 예측([78]), 폐기종 정량화([5]), STAS(air space spread) 예측([45]), 그리고 ATTR-CM 조기 발견([31]) 등에서 높은 성능을 보이지만, 실제 임상 현장에서의 광범위한 적용과 표준화에는 아직 거리가 있습니다. 특히, PET/CT 기반 follicular lymphoma의 POD24 및 골수 침윤 예측 모델([57], [58]), 유방 MRI triage를 위한 foundation model([63]), 그리고 CT topogram 기반 해부학적 라벨링([50]) 등 다양한 AI 도구가 개발되었으나, 다기관 전향적 검증과 표준화된 파이프라인 구축이 여전히 필요한 것으로 지적됩니다([54]). 또한, neoadjuvant therapy 후의 병리학적 반응을 평가하기 위한 AI 기반 %RVT 점수([9])와 tumor bed stroma 정량화([29])는 기존 수동 평가의 한계를 보완할 잠재력이 있으나, 임상적 유효성 입증과 규제 승인 과정에서의 장벽이 존재합니다.

4. 희귀 또는 난치성 아형(Rare/Refractory Subtypes)에 대한 표적 치료 옵션의 제한 특정 유전자 변이나 병리학적 아형을 가진 환자군에서 치료 선택지가 제한적이거나 내성이 빠르게 발생하는 문제가 있습니다. EGFR Exon 20 Insertion Mutations(NSCLC)은 Sunvozertinib으로 새로운 표준이 제시되었으나([1]), 여전히 다른 희귀 변이(예: BRAF fusions, MYO5C-ALK fusion)에 대한 최적의 치료 전략([52], [75])이 확립되지 않았습니다. 또한, SCLC로 전환된 EGFR-mutant NSCLC(T-SCLC) 환자([33], [41])와 platinum-resistant 난소암([47]), castration-resistant prostate cancer([71]) 등에서 기존 요법에 대한 내성이 고조되며, 새로운 표적(예: RAS signaling inhibitors combined with radiotherapy/immunotherapy [79]) 또는 세포 치료(CAR-NK, CAR-T)의 효능을 높이는 전략이 절실히 요구됩니다.

5. 신약 개발 및 임상 시험에서의 안전성 관리 및 부작용 예측 모델 부족 새로운 치료법(ADC, Immunotherapy, Cell therapy) 도입과 함께 나타나는 독특한 부작용 프로파일 관리가 중요한 unmet need입니다. ADC 치료 관련 간질성 폐질환(ILD) 및 pneumonitis의 치명적 위험([21])과 SBRT+atezolizumab 조합에서의 Grade 3 이상 부작용 증가([8])는 안전성 모니터링의 중요성을 강조합니다. 또한, CAR-T/NK 세포 치료에서 종양 미세환경에 의한 기능 억제([67], [14])와 sarcoma에서의 TIGIT blockade 국소 투여 필요성([74])은 치료 최적화를 위한 정교한 부작용 관리 및 효능 증진 전략이 필요함을 시사합니다.

우선순위 제언

제공된 문헌을 종합할 때, 가장 시급하고 반복적으로 지적되는 gap은 "종양 미세환경(TME) 매개 면역 회피 기전의 표적화"와 "AI 기반 비침습적 바이오마커의 임상 표준화"입니다.

  1. TME 표적 병용 요법 개발: anti-PD-1/PD-L1 내성을 유발하는 특정 세포(예: TAMs, MDSCs, Neutrophils) 및 분자 경로(예: CXCR2, AARS1 lactylation, N-glycan, PGE2/EP receptors)를 표적으로 하는 억제제 또는 조절제를 기존 면역요법과 병용하는 전략이 다수 암종(NSCLC, HCC, BC, GC)에서 공통적으로 제시되고 있습니다([7], [13], [14], [16], [18], [20], [36], [40], [44], [53], [64], [67]). 이는 단순한 checkpoint blockade를 넘어 TME를 재프로그래밍하는 차세대 면역치료의 핵심 방향입니다.
  2. AI/Radiomics 기반 정밀 의학 도구 검증: 영상 데이터(CT, MRI, PET)와 AI 알고리즘을 결합하여 종양 이질성([76], [80]), 치료 반응([9], [29], [34], [57], [58], [65]), 그리고 유전자 변이 상태([78])를 비침습적으로 예측하는 모델들이 활발히 개발되고 있으나, 다기관 전향적 연구와 표준화된 프로토콜을 통한 임상 유효성 검증이 선행되어야 실제 진료에 통합될 수 있습니다.

근거 논문

  1. First-Line Sunvozertinib in NSCLC with EGFR Exon 20 Insertion Mutations. — The New England journal of medicine, 2026-Aug-20
  2. Osimertinib With or Without Chemotherapy in Advanced Non-Small Cell Lung Cancer With EGFR and Concurrent TP53 Mutations: A Randomized Clinical Trial. — JAMA, 2026-Aug-10
  3. The changing therapeutic landscape of small-cell lung cancer. — Lancet (London, England), 2026-Sep-12
  4. PRKX-mediated stabilization of PD-L1 characterizes an immunosuppressive gastric cancer subtype. — Journal for immunotherapy of cancer, 2026-Sep-09
  5. Segmentation-based deep learning emphysema quantification using chest CT: improved accuracy and robustness vs LAA-950. — European radiology, 2026-Sep-09
  6. PREDICT-GBM: A multicenter platform advancing personalized glioblastoma radiotherapy planning. — NPJ digital medicine, 2026-Sep-09
  7. HIF1A+CSF3R+ neutrophils-dominated hypoxic niche induced metabolic reprogramming for neoadjuvant therapy resistance in NSCLC. — Journal for immunotherapy of cancer, 2026-Sep-08
  8. Induction and consolidation atezolizumab with stereotactic body radiation therapy versus radiation alone in high-risk, early-stage non-small-cell lung cancer (SWOG/NRG S1914): a multicentre, open-label, superiority, phase 3, randomised controlled trial. — Lancet (London, England), 2026-Sep-06
  9. Artificial Intelligence-Based Assessment of Pathologic Response to Neoadjuvant Chemoimmunotherapy in Non-Small Cell Lung Cancer: An International Multicenter Cohort Study. — Lung cancer (Amsterdam, Netherlands), 2026-Sep-05
  10. Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer. — The New England journal of medicine, 2026-Sep-03
  11. Spatial habitat radiomics predicts tertiary lymphoid structure status and identifies an IDO1+ migratory dendritic cell axis in breast cancer. — Journal for immunotherapy of cancer, 2026-Sep-03
  12. The efficacy and feasibility of neoadjuvant immunochemotherapy versus chemotherapy in Limited-Stage Small-Cell lung cancer. — Lung cancer (Amsterdam, Netherlands), 2026-Sep-02
  13. Targeting the PD-L1-induced PDK4/GLS metabolic axis overcomes anti-PD-1 resistance in non-small cell lung cancer. — Journal for immunotherapy of cancer, 2026-Sep-02
  14. Enhanced CD33 CAR-NK cells secreting anti-CD73scFv overcome adenosine-mediated immunosuppression and improve anti-AML efficacy. — Journal for immunotherapy of cancer, 2026-Sep-01
  15. Mechanistic modeling of tumor immune microenvironment reveals strategies to enhance antibody-drug conjugates' efficacy. — Journal for immunotherapy of cancer, 2026-Sep-01
  16. CPNE1 promotes stemness and confers resistance to GPC3 CAR-T cell therapy in hepatocellular carcinoma via the STAT3-TGF-β signaling pathway. — Journal for immunotherapy of cancer, 2026-Jul-31
  17. Cancer-associated mesothelial cells drive immune escape and therapy resistance in ovarian cancer. — Journal for immunotherapy of cancer, 2026-Jul-30
  18. CXCR2-mediated metabolic interaction between prostate cancer cells and the immunosuppressive tumor microenvironment. — Journal for immunotherapy of cancer, 2026-Jul-29
  19. Adipocyte-derived LTB4 programs human NKG2A+ γδ T cells as cytotoxic sentinels at the adipose-tumor interface in breast cancer. — Journal for immunotherapy of cancer, 2026-Jul-28
  20. In situ generation of proinflammatory CAR macrophages via mRNA-TLR agonist co-delivery for triple-negative breast cancer immunotherapy. — Journal for immunotherapy of cancer, 2026-Jul-28
  21. Interstitial lung disease in patients treated with antibody-drug conjugates: a review. — Lung cancer (Amsterdam, Netherlands), 2026-Jul-11
  22. Neoadjuvant and perioperative chemo-immunotherapy in early-stage non-small cell lung cancer: international expert panel meeting by AIOT. — Lung cancer (Amsterdam, Netherlands), 2026-Jul-11
  23. Ensartinib in Resected ALK-Positive Non-Small-Cell Lung Cancer. — The New England journal of medicine, 2026-Jul-09
  24. Selpercatinib Improves EFS in RET Fusion-Positive NSCLC. — Cancer discovery, 2026-Jul-01
  25. Ternary classification prediction and heterogeneity quantification for HER2-Zero, -low, and -positive in breast cancer using HER2-targeted PET/CT imaging. — European journal of nuclear medicine and molecular imaging, 2026-Jul
  26. IL20RB drives non-small cell lung cancer progression and immune evasion via K267‑dependent activation of JAK2 phosphorylation and STAT3 signaling. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-31
  27. Clinical outcomes and genomic features of uncommon EGFR exon 19 deletion subtypes in osimertinib-treated non-small cell lung cancer. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-31
  28. Adjuvant immunotherapy in resectable non-small cell lung cancer with nodal downstaging. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-31
  29. Artificial intelligence-based assessment of tumor bed stroma in non-small cell lung cancer after neoadjuvant therapy: Association with pathologic response and survival. A multicenter study. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-31
  30. MTAP loss in non-small-cell lung Cancer and beyond: Therapeutic targeting of the MAT2A-PRMT5 axis. — Cancer treatment reviews, 2026-Aug-29
  31. Electrocardiogram-Based Deep Learning to Prioritize Testing for Transthyretin Amyloid Cardiomyopathy. — JAMA, 2026-Aug-28
  32. AdvanTIG-301: a phase III study of ociperlimab plus tislelizumab and concurrent chemoradiotherapy in stage III unresectable non-small cell lung cancer. — Journal for immunotherapy of cancer, 2026-Aug-26
  33. Adding immunotherapy to chemotherapy may improve survival after SCLC transformation in EGFR-mutant NSCLC: a multicenter real-world study. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-23
  34. RaFiST: a radiomics model for non-invasive stratification of tumor fibrosis and prognostic prediction in non-small cell lung cancer. — European radiology, 2026-Aug-20
  35. DNA hypomethylation identifying clinical benefit subgroup of small-cell lung cancer: multi-omics analysis of a phase II trial with durvalumab plus olaparib as maintenance therapy. — Journal for immunotherapy of cancer, 2026-Aug-14
  36. AARS1-mediated lactylation reprograms macrophage lipid metabolism to restrict antitumor immunity. — Journal for immunotherapy of cancer, 2026-Aug-14
  37. A phase 2 study of encorafenib in combination with binimetinib for Chinese participants with BRAFV600E mutated metastatic non-small cell lung cancer: Results from the OCEAN II study. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-13
  38. Efficacy and prognostic analysis of induction chemoimmunotherapy in unresectable stage Ⅲ non-small cell lung cancer: a single-center retrospective study. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-13
  39. Survival According to Radiomic and Visual UIP Classification in Fibrotic ILD. — Chest, 2026-Aug-12
  40. PGE2-mediated NK cell reprogramming drives acquired immunotherapy resistance in lung adenocarcinoma. — Journal for immunotherapy of cancer, 2026-Aug-12
  41. Genomic Profiling, Risk Stratification, and Post-Transformation Treatment Outcomes in Patients with Transformed Small-Cell Lung Cancer: A Multicenter Analysis. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-09
  42. Loss of NCCRP1 overcomes immune evasion in lung adenocarcinoma. — Journal for immunotherapy of cancer, 2026-Aug-05
  43. β-glucan elicits APOE-dependent peripheral trained immunity to suppress hepatocellular carcinoma. — Journal for immunotherapy of cancer, 2026-Aug-04
  44. TGF-β1 drives neutrophil extracellular traps formation to promote CD8+ T cell exhaustion via the ERK-c-Fos-JunB axis, mediating gastric cancer immunotherapy resistance. — Journal for immunotherapy of cancer, 2026-Aug-04
  45. DAFNet: A multi-modal deep learning model based on whole-lung CT for the automated prediction of the air space spread of lung adenocarcinoma. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-01
  46. Deep learning image reconstruction for 50-keV virtual monoenergetic dual-energy CT of the thyroid: a prospective "dual-low" dose study. — European radiology, 2026-Sep-09
  47. Transcriptomic analysis of a phase 1 trial for intraperitoneal monocytes plus IFNs in ovarian cancer reveals support and recruitment of cell-mediated immunity. — Journal for immunotherapy of cancer, 2026-Sep-07
  48. TAMing the tumor: targeting immune inhibitory receptors on tumor-associated macrophages in pediatric brain tumors - an emerging immunotherapy strategy. — Journal for immunotherapy of cancer, 2026-Sep-07
  49. Treatment-free interval as a determinant of second-line chemotherapy outcomes in extensive-stage small cell lung cancer: a Dutch population-based study. — Lung cancer (Amsterdam, Netherlands), 2026-Sep-05
  50. Topogram-based anatomical labelling of CT series: anatomy-aware CT data processing using deep learning. — European radiology, 2026-Sep-03
  51. Subtyping limited stage small cell lung cancer (LS SCLC) reveals inflammatory subtypes with improved chemoradiotherapy outcomes. — Lung cancer (Amsterdam, Netherlands), 2026-Sep-02
  52. BRAF fusions define therapeutic vulnerability and tyrosine kinase inhibitor resistance in non-small cell lung cancer. — Lung cancer (Amsterdam, Netherlands), 2026-Jul-30
  53. Myosin VI drives breast cancer progression via SP1/CA9-mediated acidic tumor microenvironment remodeling and subsequent M2 macrophage polarization. — Journal for immunotherapy of cancer, 2026-Jul-30
  54. Pericoronary fat radiomics on coronary CT angiography for predicting major adverse cardiac events: a systematic review and meta-analysis. — European radiology, 2026-Jul-28
  55. Development and validation of a risk-stratification model for individualized management of leptomeningeal metastases in EGFR- mutant NSCLC (LM-Index). — Lung cancer (Amsterdam, Netherlands), 2026-Jul-21
  56. A Circulating GPNMB-Based Multimodal Model Integrates Tumor-Immune Crosstalk to Predict Immunotherapy Response in Esophageal Cancer. — Cancer discovery, 2026-Jul-01
  57. A deep learning PET/CT biomarker for early progression (POD24) and survival stratification in follicular lymphoma: a multicenter study. — European journal of nuclear medicine and molecular imaging, 2026-Jul
  58. An interpretable PET/CT-based radiomic-clinical model for predicting bone marrow involvement in follicular lymphoma: comparison of pelvic and spine-pelvis VOI frameworks. — European journal of nuclear medicine and molecular imaging, 2026-Jul
  59. Fusion isoform multiplicity and impact on treatment outcomes in ALK-rearranged non-small cell lung cancer with next-generation tyrosine kinase inhibitors. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-26
  60. Therapeutic evolution: Adoption of newly approved systemic therapies in resected stage IB-IIIA NSCLC in the United States. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-20
  61. Treatment patterns and outcomes in advanced and metastatic lung cancer in France: Results from the Epidemiological Strategy and medical Economics (ESME) database lung cancer in France. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-19
  62. T cells are critical for pre-metastatic niche formation through the STAT3/IL-17 axis. — Journal for immunotherapy of cancer, 2026-Aug-14
  63. Adapted foundation models for breast MRI triaging in contrast-enhanced and non-contrast-enhanced protocols. — European radiology, 2026-Aug-13
  64. Turning off methylglyoxal stress: an alternative approach to inhibit MDSC expansion and metastasis in triple-negative breast cancer. — Journal for immunotherapy of cancer, 2026-Aug-13
  65. ΔAverage of long and short axis diameter on non-contrast CT is associated with major pathological response to neoadjuvant immunotherapy in resectable non-small cell lung cancer. — European radiology, 2026-Aug-13
  66. Treatment-stratified associations of pathological complete response with survival in resected limited-stage small cell lung cancer: A multicenter retrospective study with exploratory spatial immune profiling. — Lung cancer (Amsterdam, Netherlands), 2026-Aug-12
  67. N-glycans in non-malignant tumor microenvironment cells dampen CAR-T cell function in solid tumors. — Journal for immunotherapy of cancer, 2026-Aug-12
  68. Targeting GRP75 by natural compound polyphyllin II triggers mitochondrial calcium overload and pyroptosis to potentiate cancer immunotherapy. — Journal for immunotherapy of cancer, 2026-Aug-06
  69. Tumor stroma-immune interactions shape the immunosuppressive microenvironment and predict response to neoadjuvant chemoradiotherapy plus immunotherapy in rectal cancer. — Journal for immunotherapy of cancer, 2026-Aug-03
  70. ULK1, a novel therapeutic target to delay drug tolerance to EGFR-TKIs in an EGFR-mutant non-small cell lung cancer model. — Lung cancer (Amsterdam, Netherlands), 2026-Jun-30
  71. Durable responses to triplet immunotherapy targeting TGF-β, PD-L1, and tumor antigen, with an IL-15 receptor superagonist in mismatch repair proficient castration-resistant prostate cancer. — Journal for immunotherapy of cancer, 2026-Jul-24
  72. Personalized tumor-loaded monocyte-derived dendritic cell vaccination in combination with atezolizumab as maintenance treatment in extensive-stage small cell lung cancer (ES-SCLC): phase Ib-II VENEZOLUNG trial. — Journal for immunotherapy of cancer, 2026-Jul-24
  73. Therapy-induced senescence rewires the melanoma secretome to promote antitumor immune response and augment cell therapies. — Journal for immunotherapy of cancer, 2026-Jul-22
  74. Intratumoral TIGIT blockade augments antitumor responses and bypasses increased functionality of peripheral TIGIT+ NK cells in mouse and human models of bone and soft tissue sarcoma. — Journal for immunotherapy of cancer, 2026-Jul-22
  75. A novel MYO5C-ALK fusion in lung adenocarcinoma: limited alectinib response and durable lorlatinib benefit. — Lung cancer (Amsterdam, Netherlands), 2026-Jul-21
  76. AI-driven tumor heterogeneity quantification and survival prediction in pancreatic ductal adenocarcinoma. — NPJ digital medicine, 2026-Jul-20
  77. Does OptiTROP-Lung05 open a new frontier for first-line ADC-ICI combinations in NSCLC? — Nature reviews. Clinical oncology, 2026-Jul-20
  78. Multi-task deep learning model for predicting EGFR mutation status in NSCLC. — NPJ digital medicine, 2026-Jul-20
  79. RAS signaling at the crossroads of radioresistance and tumor immunity. — Journal for immunotherapy of cancer, 2026-Jul-17
  80. Spatial architecture of tertiary lymphoid structures represents an independent prognostic dimension in hepatocellular carcinoma. — Journal for immunotherapy of cancer, 2026-Jul-17