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Welcome to the Sonoshita laboratory!


Cancer is a devastating health problem especially in developed countries, despite substantial research advances. Our lab started in 2018, and we aim to understand the mechanisms of cancer development, to identify novel therapeutic targets for cancers, and to generate effective anti-cancer therapeutics. To this end, we are employing a collaborative multidisciplinary strategy combining genetics, biochemistry, molecular biology, cell biology and medicinal chemistry, leveraging Drosophila and mammalian cancer models.

We are now seeking graduate students and JSPS postdocs who are willing to tackle cancers with us. Please feel free to contact us at: msonoshita[at] if you are interested.


PI: Prof. Masahiro Sonoshita, PhD.


(1) Dissecting colorectal carcinogenesis


Fig.1: The mechanisms of colorectal carcinogenesis.​ 

COX-2 produces bioactive lipid PGE2 to stimulate tumor angiogenesis through EP2 receptor enhancing adenoma growth. While, Notch signaling activates ABL that phosphorylates Rho-GEF TRIO to enhance cell motility driving malignant progression of the tumor. LOF, loss of function. i, inhibitor. ant, antagonist.


1.   Takaku, Sonoshita et al. J Biol Chem 1999.

2.   Sonoshita et al.Nature Med 2001.

3.   Sonoshita et al. Cancer Res 2002.

4.   Taketo & SonoshitaBiochim Biophys Acta 2002.

5.   Takeda, Sonoshita et al. Cancer Res 2003.

6.   Sonoshita et al. Cancer Cell 2011.

7.   Sonoshita et al. Cancer Discov 2015.

8.   Itatani, Sonoshita et al. J Biochem 2016.

9.   Kakizaki, Sonoshita et al. Cancer Sci 2016.

10. Okada, Sonoshita et al. Cancer Sci 2017.


Fig 2: Progression of Apc-mutant tumors upon Aes inactivation in mouse intestines.

Knocking out Apc gene initiates adenoma growth (A). Addition of epithelium-specific Aes mutation causes massive invasion of tumor glands into underlying muscle layer (B). cKO, conditional knockout. Arrowhead, invading tumor gland. MP, muscularis propria. Se, serosa.

Ref: Sonoshita et al. Cancer Cell 2011.

(2) Drug discovery


Fig 3: A whole-animal platform for developing anti-cancer drugs.

We have demonstrated that Drosophila offers an excellent platform for cancer research and drug discovery. Chemical genetic screening in a Drosophila cancer model identifies 'anti-targets', inhibition of which causes side effects by an existing drug. Following computation and medicinal chemistry utilizing these information predicts and generates candidate chemicals as novel lead molecules that do not hit anti-targets any more. Resulting novel leads show much lower toxicity in mouse models for human cancers. 

Ref: Sonoshita & Cagan. Curr Top Dev Biol 2017; Sonoshita et al. Nat Chem Biol 2018; Ung*, Sonoshita* et al. PLoS Comput Biol 2019.


Fig 4: A Drosophila model for medullary thyroid cancer (MTC).

​In larva, patched (ptc) promoter activity is useful to mark the central region of wing disc (red margin), a tissue that generates wings in adults. When a mutant active form of Ret (Ret*; found in MTC patients) is present, cells transform to proliferate, lose cell polarity, and migrate away from the original domain (arrowheads). 

Ref: Sonoshita et al. Nat Chem Biol 2018.


Fig 5: A novel lead A645 shows superior anti-cancer effect in a xenograft mouse model for MTC.

​Waterfall plot showing tumor volume change of xenografted human MTC cells (TT) in mice, as compared to pre-dosing with each bar representing one mouse. Dosing a novel lead chemical A645 reduced tumor volume more efficiently than cabozantinib (cabo), approved MTC drug, or sorafenib (soraf), the parent drug of A645, at the same doses. A645 also showed remarkably reduced toxicity as compared to soraf. Asterisk, complete remission. 

Ref: Sonoshita et al. Nat Chem Biol 2018.

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