Kanazawa University Cancer Research Institute
Isozaki Lab
- Genome Biology -
Publications
Therapy-induced APOBEC3A drives evolution of persistent cancer cells
Nature 2023 Aug;620(7973):393-401.
During targeted therapy, cancer cells evolve along with the accumulation of somatic mutations. We found that cytidine deaminase APOBEC3A is induced in response to targeted therapy, resulting in a higher tumor mutation burden after treatment. Inhibiting APOBEC3A delays acquired resistance, a potential new therapeutic strategy to prevent acquired drug resistance.
Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion
Cancer Discov. 2018 Dec;8(12):1529-1539.
In a comprehensive genomic study of EGFR mutated non-small cell lung cancer, we found novel fusion genes in osimertinib-resistant patients. We demonstrated that RET fusion gene conders resistance to osimertinib using in vitro models. A clinical trial showed the efficacy of RET inhibitor BLU-667 in two osimertinib-resistant patients.
Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial
Thorac Cancer. 2021 Mar;12(5):643-649.
The Okayama Lung Cancer Study Group completed a phase ll clinical trial Dr. Isozaki designed in Clin. Lung Cancer. 2016. We demonstrated 33.3% overall response rate of crizotinib in alectinib-refractory ALK-positive NSCLC patients.
Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non-Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405)
Clin. Lung Cancer. 2016 Nov;17(6):602-605.
Based on the findings in Cancer Res. 2016, Dr. Isozaki designed a protocol for phase ll clinical trial for alectinib-refractory NSCLC patients with EML4-ALK fusion gene. Crizotinib (ALK/MET inhibitor) monotherapy for alectinib-resistant patients was proposesd.
Non-small cell lung cancer cells acquire resistance to the ALK inhibitor alectinib by activating alternative receptor tyrosine kinases
Cancer Res. 2016 Mar;15;76(6):1506-16.
We elucidated two novel resistance mechanisms of ALK inhibitor alectinib in non-small cell lung cancer: (1) loss of ALK and activation of insulin-like growth factor 1 receptor (IGF1R) and (2) hyper-autocrine of hepatocyte growth factor (HGF).
Publication list
Haratake N, Ozawa H, Morimoto Y, Yamashita N, Daimon T, Bhattacharya A, Wang K, Nakashoji A, Isozaki H, Shimokawa M, Kikutake C, Suyama M, Hashinokuchi A, Takada K, Takenaka T, Yoshizumi T, Mitsudomi T, Hata AN, Kufe D. "MUC1-C is a common driver of acquired osimertinib resistance in NSCLC." J Thorac Oncol. 2023 Nov;3(23)02348-1.
#Isozaki H, Sakhtemani R, Abbasi A, Nikpour N, Stanzione M, Oh S, Langenbucher A, Monroe S, Su W, Cabanos HF, Siddiqui, FM, Phan N, Jalili P, Timonina D, Bilton S, Gomez-Caraballo M, Archibald HL, Nangia V, Dionne K, Riley A, Lawlor M, Banwait MK, Cobb RG, Zou L, Nicholas NJ, Ott CJ, Benes C, Getz G, Chan CS, Shaw AT, Gainor JF, Lin JJ, Sequist LV, Piotrowska Z, Yeap BY, Engelman JA, Lee JK, Maruvka YE, Buisson R, ¨Lawrence MS, ¨Hata AN. "Therapy-induced APOBEC3A drives evolution of persistent cancer cells." Nature 2023. Aug;620(7973):393-401.
Harada D*, Isozaki H*, Kozuki T, Yokoyama T, Yoshioka H, Bessho A, Hosokawa S, Takata I, Takigawa N, Hotta K, Kiura K, Okayama Lung Cancer Study Group. "Crizotinib for recurring non-small-cell lung cancer with EML4-ALK fusion genes previously treated with alectinib: A phase II trial." Thorac Cancer. 2021 Mar;12(5):643-649.
Piotrowska Z*, Isozaki H*, Lennerz JK, Gainor JF, Lennes IT, Zhu VW, Marcoux N, Banwait MK, Digumarthy SR, Su W, Yoda S, Riley AK, Nangia V, Lin JJ, Nagy RJ, Lanman RB, Dias-Santagata D, Mino-Kenudson M, Iafrate AJ, Heist RS, Shaw AT, Evans EK, Clifford C, Ou SI, Wolf B, Hata AN, Sequist LV. "Landscape of acquired resistance to osimertinib in EGFR-mutant NSCLC and clinical validation of combined EGFR and RET inhibition with osimertinib and BLU-667 for acquired RET fusion." Cancer Discov. 2018 Dec;8(12):1529-1539.
Isozaki H, Hotta K, Ichihara E, Takigawa N, Ohashi K, Kubo T, Ninomiya T, Ninomiya K, Oda N, Yoshioka H, Ichikawa H, Inoue M, Takata I, Shibayama T, Kuyama S, Sugimoto K, Harada D, Harita S, Sendo T, Tanimoto M, Kiura K. "Protocol Design for the Bench to Bed Trial in Alectinib-Refractory Non-Small-Cell Lung Cancer Patients Harboring the EML4-ALK Fusion Gene (ALRIGHT/OLCSG1405)." Clin. Lung Cancer. 2016 Nov;17(6):602-605.
Ochi N, Isozaki H, Takeyama M, Singer JW, Yamane H, Honda Y, Kiura K, Takigawa N. "Synergistic effect of pacritinib with erlotinib on JAK2-mediated resistance in epidermal growth factor receptor mutation-positive non-small cell lung cancer." Experimental Cell Research. 2016 Jun;344 (2), 194-200.
Isozaki H, Ichihara E, Takigawa N, Ohashi K, Ochi N, Yasugi M, Ninomiya T, Yamane H, Hotta K, Sakai K, Matsumoto K, Hosokawa S, Bessho A, Sendo T, Tanimoto M, and Kiura K. "Non-small cell lung cancer cells acquire resistance to the ALK inhibitor alectinib by activating alternative receptor tyrosine kinases." Cancer Res. 2016 Mar;15;76(6):1506-16.
Isozaki H, Takigawa N, Kiura K. “Mechanisms of Acquired Resistance to ALK Inhibitors and the Rationale for Treating ALK-positive Lung Cancer.” Cancers (Basel). 2015 Apr;7(2):763-83.
Minami D, Takigawa N, Kato Y, Kudo K, Isozaki H, Hashida S, Harada D, Ochi N, Fujii M, Kubo T, Ohashi K, Sato A, Tanaka T, Hotta K, Tabata M, Toyooka S, Tanimoto M, Kiura K. "Downregulation of TBXAS1 in an iron-induced malignant mesothelioma model." Cancer Sci. 2015 Oct;106(10):1296-302.
Yamane H, Isozaki H, Takeyama M, Ochi N, Kudo K, Honda Y, Yamagishi T, Kubo T, Kiura K, Takigawa. N. "Programmed cell death protein 1 and programmed death-ligand 1 are expressed on the surface of some small-cell lung cancer lines." Am J Cancer Res. 2015 Mar 15;5(4):1553-7.
Ochi N, Yamane H, Hotta K, Fujii H, Isozaki H, Honda Y, Yamagishi T, Kubo T, Tanimoto M, Kiura K, Takigawa N. "Cisplatin-induced hyponatremia in malignancy: comparison between brand-name and generic formulation." Drug Des Devel Ther. 2014 Dec;8:2401-8.
Isozaki H, Yasugi M, Takigawa N, Hotta K, Ichihara E, Taniguchi A, Toyooka S, Hashida S, Sendo T, Tanimoto M, Kiura K." A new human lung adenocarcinoma cell line harboring the EML4-ALK fusion gene." Jpn J Clin Oncol. 2014 Oct;44(10):963-8.
Yamane H, Ochi N, Isozaki H, Yamagishi T, Honda Y, Takigawa N. "Skin involvement in diffuse large B-cell lymphoma detected using positron emission tomography." Thoracic Cancer. 2014 Nov;5 (6), 581.
Isozaki H, Sato T, Kawasaki Y, Fujiwara S, Ueshima S, Honda N, Ichihara E, Hotta K, Takigawa N, Tabata M, Kiura K, Tanimoto M, Sendo T. "Safety and tolerability of short hydration regimen for cisplatin-based chemotherapy in patients with lung cancer." Jan J Pharm Health Sci. 2012 Mar;38(3)184-90.
* co-first author
# co-rresponding author