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J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 5 of 27

Results: PI3K-C2γ loss was modeled by deleting PIK3C2G gene in a mouse model of pancreatic cancer
(KPC). We found that its PI3K-C2γ loss was sufficient to initiate and promote pancreatic tumor development,
strongly reducing mice survival rate (18 weeks vs. 36 weeks) and driving rapid progression to PDAC. In
pancreatic tumors reduced expression of PI3K-C2γ expression was significantly associated with poor
survival and resistance to chemotherapy. We reported that lysosomal localization of PI3K-C2γ is responsible
for mTORC1 inhibition under conditions of serum deprivation. In addition, we also observed that PI3K-C2γ
loss promotes the metabolic rewiring of PDAC, through the control of several metabolic factors, including
glucose and monocarboxylate transporters and glycolytic enzymes (PKM2, HK2 and LDH). Furthermore,
the use of rapalogs in KO KPC delay tumor progression.

Conclusion: PI3K-C2γ is a novel tumor suppressor in pancreatic cancer and the metabolic phenotype of
PI3K-C2γ-deficient tumors can be exploited for specific therapeutic strategies.

6. Alleviating the Warburg effect: preliminary clinical results in advanced malignancies

resistant to chemotherapy

Laurent Schwartz

Assistance Publique des hôpitaux de Paris, 3 avenue Victoria, Paris 75004, France.

Chlorine dioxide and Methylene blue are known generators of free radicals. These free radicals are known to
enhance the efficacy of the mitochondria.

The goal of this abstract is to describe the first fourteen patients with advanced uncurable cancer treated,
with a combination of metabolic treatment (lipoic acid, hydroxycitrate) and chlorine dioxide. All but one
patient had failed conventional chemotherapy. Only three patients underwent concomitant conventional
chemotherapy. There was no major side effect but nausea and diarrhea. All but one patient responded to
treatment. Two more patients were treated with Methylene Blue and metabolic treatment for advanced
tumors. One had low dose chemotherapy, the other one, with metastatic pancreatic cancer had no other
treatment. Both responded. Rigourous clinical trials are warranted.

7. Ketogenic diets during radiotherapy against cancer

Rainer J. Klement

Department of Radiation Oncology, Leopoldina Hospital Schweinfurt, Robert-Koch-Straße 10, Schweinfurt
97422, Germany.

The altered glucose metabolism of tumor cells is a long-known phenomenon that also contributes to
resistance against radiotherapy by securing ATP production important for DNA repair, promoting tumor
repopulation and increasing the pool of anti-oxidative molecules for protection against reactive oxygen
and nitrogen species (ROS/RNS). In theory therefore, impairing the glucose metabolism of cancer cells
is expected to lead to radiosensitization. Deduced from the hypothesis that cancer is a metabolic disease
with mitochondrial dysfunction a hallmark of most tumor cells, ketogenic diets - i.e., diets systemically
downregulating glycolysis and supporting ketone body and fat oxidation - have been proposed to selectively
target tumor cells which in contrast to normal cells would be weakened when glucose and insulin levels
are reduced. While many preclinical studies indeed found evidence for a reduction of tumor glycolytic