Technology from Kyoto University
A Plasma Biomarker for Hypoxic Fraction in Solid Tumors
We are looking to out-license the technology for its commercialization.

Plasma SPINK1 levels are correlated with the volume of hypoxic fractions in malignant
solid tumors.
◆ BackgroundHypoxic regions (regions with a decreased partial pressure of oxygen) in malignant solidtumors are a key environmental factor that enhances the resistance of cancer cells toradiotherapy and anticancer chemotherapy. Lower oxygen levels in tumors are also
known to be associated with advanced malignancy. Therefore, assessing the volume ofhypoxic regions and the degree of hypoxia in tumor tissues is critical not only formonitoring their pathological conditions and predicting therapeutic effects on them but
also for developing a novel strategy for personalized cancer therapy. However, currently
available methods to detect hypoxia are invasive such as PET imaging and IHC on biopsy.

◆ Development Status
Verified in vitro / in vivo:
・ Hypoxia-stimulated
cells

express

cancerSPINK1andsecrete SPINK1 into the blood.
・The concentration of SPINK1
secreted into the plasma can beused as an indicator to monitor
the hypoxic volumes in the◆ Descriptiontumor.

Researchers at Kyoto University found that the expression and secretion of SPINK1 are・ Pancreatic cancer patients

immediately increased upon severe but not mild hypoxia and returned to their basal

withlevels after reoxygenation (Fig. 1). In addition, they found a positive correlation between

levels show lower survival rates.

higherplasma

SPINK1the levels of SPINK1 in plasma and the volume of hypoxia in the tumors (Fig. 2).
Furthermore, they confirmed that SPINK1 increases the radioresistance of cancer cells(Fig. 3). These findings suggest that SPINK1 can be used as a “minimally invasive◆ Publication

plasma biomarker" to monitor "tumor hypoxia" and "tumor malignancy".

Suwa et al., JCI Insight (2021)
https://doi.org/10.1172/jci.insight

SPINK1 mRNA levels(/β-actin)

C.148135.

SPINK1 protein levels
in medium (pg/mL protein)B

SPINK1 mRNA levels(/β-actin)A◆ Application•

In vitro diagnostic reagents•

Reagents•

Drug discovery (therapeutictargets)◆ OfferFig. 1 Cancer cells stimulated by hypoxia express and secrete SPINK1
A human cervical carcinoma cell line, HeLa cells, expressed (A, B) and secreted (C) SPINK1 upon hypoxic stimulus. The hypoxiadependent expression returned to the basal levels upon reoxygenation treatment (B).

AA

SPINK1 conc.
in plasma (pg/ml)

SPINK1 conc.
In plasma (pg/ml)

Fig. 2 The volume of hypoxic regions in malignant
solid tumors is correlated with the concentration of
SPINK1 in plasma.
Tumor xenografts with various hypoxic fraction were produced byadministrating a hemolytic agent (phenylhydrazine) into tumorbearing mice with a HeLa xenograft. The concentration of SPINK1 inthe plasma did not correlate with tumor volume (A, R2 = 0.0658), but
strongly correlated with the hypoxic fractions in tumor tissues whichwere monitored as the levels of endogenous hypoxia marker, CA9(B, R2 = 0.7444).

License•Option for license◆ Contact
Technology Transfer Team,
Kyoto University Division
TLO-KYOTO Co., Ltd.

SPINK1B•

Mail: event@tlo-kyoto.co.jp
Phone: +81-75-753-9150

BLevel 5, International Science
Innovation Bldg., Kyoto University,
Yoshidahonmachi, Sakyo-ku,Kyoto
606-8501, JapanSPINK1 (0 Gy)
SPINK1 (10 Gy)

Fig. 3 SPINK1 promotes the radioresistance ofcancer cells.
(A) Colony formation assay confirmed that HeLa cells transfectedwith SPINK1-expressing vector acquired more radioresistance thanthose transfected with an empty vector (EV). (B). Tumor-bearing
mice transplanted with the SPINK1-expressing HeLa cells were
subjected to local treatment with gamma rays and subsequent
tumor growth was measured. Overexpression of SPINK1
accelerated tumor regrowth after radiotherapy.