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Researchers: Prof. Fuad Fares; Dr. Lital Sharvit

Discovering a novel treatment for pancreatic cancer with a mushroom-derived compound.

Background

Pancreatic cancer is one of the deadliest of all solid malignancies. There are generally no symptoms during the early stages of this cancer, so by the time it is diagnosed it has reached advanced stages. It has one of the worst prognosis of all cancers, with a 6% 5-year survival rate. The majority of pancreatic cancer patients die within the first year of diagnosis.

The current chemotherapy treatment, either alone or in combination with radiation, has been proven to improve progression-free survival (that is, the time that a patient lives with the disease but it does not get worse) by less than a year.

Pancreatic cancer prevalence worldwide is 4.1 per 100,000, according to the World Cancer Research Fund International. The disease is the twelfth most common cancer and the seventh most common cause of death from cancer.

Hope for a Cure from a Mushroom-Derived Compound

Historically, drugs have primarily been derived from plant, animal and mineral sources. Within that realm, mushrooms comprise a vast and yet largely unexploited source for powerful new compounds. Many forms of mushrooms have been found to contain a variety of secondary metabolites with antitumor properties.

University of Haifa Faculty of Natural Sciences researchers Prof. Fuad Fares and Dr. Lital Sharvit are in the advanced stages of research leading toward the development of a novel treatment for pancreatic cancer, based on the properties of a mushroom-derived compound that they discovered in a species endemic to Israel.

Research Status

Prof. Fares and Dr. Sharvit have successfully advanced their research to inhibit the growth of human pancreatic cancer cells in vitro and in vivo. Using the mushroom-derived compound, a significant tumor growth decrease due to induction of apoptosis (cell death) is achieved. In vivo results have confirmed the in vitro findings, destroying more than 90 percent of the treated cancer cells in both environments. Furthermore, animal testing has shown significant tumor growth inhibition with no adverse effects in body weight or in liver and kidney functions. This indicates the compound’s safe and effective value in impeding pancreatic cancer tumor progression.
Synthesis of this active compound controlling the apoptosis process can be used to develop novel and effective strategy for pancreatic cancer treatment.

Mushroom derived compound leading to development of a novel treatment for pancreatic cancer.

Carmel established CanCurX Ltd. to advance and commercialize this technology, with a seed investment from the Carmel Innovations Fund.

Investment opportunities

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Related pages 

CanCuRX Ltd.

Fuad Fares, Prof. - researcher page

Researchers: Dr. Dalit Barkan Dr. Amiram Ariel

Developing novel therapies for the prevention and treatment of recurrent metastatic breast cancer

Background

Distant recurrence, also known as metastasis or dissemination of the tumor cells, is the most serious type of breast cancer recurrence and is associated with significantly lower survival. Recent evidence indicates dissemination of tumor cells from the initial breast tumor to secondary organs may be an early event in the disease process. These disseminated tumor cells reside in the bone marrow, lymph nodes, and blood circulation of breast cancer patients and lie dormant (as non-dividing cells). They do not respond to chemotherapy or radiotherapy treatments that target actively dividing cells and cannot be detected with diagnostic imaging, lingering in the body as a ticking time bomb. Hence, the continuous presence of disseminated dormant tumor cells even after treatment may account in part for the latency and subsequent outgrowth of the cells 5-20 years after initial treatment.

Developing Novel Therapy for the Prevention and Treatment of Metastatic Breast Cancer

Dr. Dalit Barkan and Dr. Amiram Ariel from the Department of Human Biology at the University of Haifa have been making breakthrough advances in developing a novel approach to fight metastatic growth. Their work is founded on understanding the processes that promote reactivation of dormant cancer cells and their proliferation as a metastatic disease following a long period of inactivity.
Ultimately, Barkan and Ariel expect their work to validate and optimize novel, cutting edge therapeutics for metastatic cancer recurrence

Research Status
Dr. Barkan recently demonstrated that changes occurring in the tissue where the dormant tumor cells reside promotes their outgrowth. The tissue changes resemble scarred tissue (fibrotic-like tissue). Based on these findings Dr. Barkan and Dr. Ariel developed novel white blood cells (macrophages) that can prevent the formation of the fibrotic-like tissue and in turn inhibit the outgrowth of dormant tumor cells.
Animal trials have shown successful treatment in female mice, encouraging the team to continue developing novel therapies for prevention and treatment of metastatic breast cancer.

The novel technology platform holds the potential for discovery and development of therapies for the prevention and treatment of metastatic breast cancer.

Market potential [link to company page - anchor]

Researcher : Dr. Amiram Ariel

Background

Macrophages are specialized immune cells involved in the healing process following inflammatory insults. Macrophage bioactivity can promote the natural resolution of inflammation and so that tissue can return to its normal function. However, microphage bioactivity can also result in tissue fibrosis and irreversible damage to the affected organ. The exact outcome of the inflammatory process depends on the mediators secreted by macrophages during its resolution.

Tissue fibrosis is a pathology that is not adequately addressed by currently marketed drugs.

Drug Development
for Prevention and Treatment of Fibrosis
Lactoferrin (Lf) is a host defense protein found in milk, colostrum, saliva, tears, mucus secretions and leukocyte granules. The Lf protein possess anti-microbial, anti-viral, anti-parasite, anti-inflammatory and anti-cancer activities. Nutraceutical products of lactoferrin are marketed as food supplements.

Research conducted by Dr. Amiram Ariel, head of the University of Haifa's Laboratory for Molecular Pathways in the Resolution of Inflammation, is examining whether Lf-derived peptides generated by macrophages can promote non-fibrotic healing and prevent fibrosis in various organs (i.e., liver, lung, kidney, skin, etc.).

Research Status
Macrophages acquire Lf from apoptotic neutrophils during the resolution of inflammation and process it to shorter fragments. Dr. Amiram's research has found that different Lf fragments associate with the onset and resolving phases of inflammation in murine and bovine models of inflammation. A 17 kDa fragment of Lf is associated with the resolution of inflammation and contains 2 immuno-modulatory peptides. One of these peptides induces an anti-inflammatory and anti-fibrotic mediator secretion profile from human macrophages.

This project addresses a molecular target that has not been previously described. This agent and the signaling pathway it triggers are perceived as novel therapeutic modules for tissue fibrosis.

Potential Applications
The developed end product is expected to serve as a treatment for debilitating inflammatory and fibrotic disorders, such as autoimmune disorders, sepsis, lung, liver, kidney, and skin fibrosis.

Investment & Partnership Opportunities
Carmel Ltd. is seeking potential partners and/or investors in this area.

Related pages:

Amiram Ariel, Dr. researcher page

CanCuRX Ltd. 

Preventing Breast Cancer Recurrence

Elucidating the molecular mechanism of ARTS-induced cell death to restore selective self-destruction of cancer cells

Main Researcher: Prof. Sarit Larisch
 

Background
All cells in our body have the ability to self-destruct by activating an intrinsic cell death program called “apoptosis”. In this way, the accumulation of damaged and potentially dangerous cells, such as tumor cells, is greatly limited.
Unfortunately, cancer cells can acquire resistance towards cell death by inactivating cell suicide pathways, thereby gaining the ability for “unlimited” life and propagation. However, the ability to undergo apoptosis is not completely lost in cancer cells and most currently used anti-cancer therapies (chemotherapy, radiation) act by activating this apoptosis death pathway in cancer cells.

ARTS-induced tumor cell death R&D
Prof. Sarit Larisch's lab focuses on investigating the molecular mechanisms of cell death, and how abnormal regulation of this process contributes to human diseases. She identified a mitochondrial pro-apoptotic protein termed ARTS (Sept4_i2) that is derived from the Sept4 septin gene by differential splicing.
Over-expression of ARTS is sufficient to promote apoptosis in many cultured tumor cells.
Conversely, the reduction of endogenous ARTS protein by anti-sense or shRNA methods can protect cells against various pro-apoptotic insults.
This indicates that ARTS is important for induction of apoptosis in a wide variety of apoptosis paradigms. A central step for the execution of apoptosis is the activation of caspases, a family of enzymes that when activated bring about the demise of the cell. Caspases are regulated by both activators and inhibitors, such as IAPs (Inhibitor of Apoptosis Proteins).
The best characterized member of this family is X-IAP (X-linked IAP). ARTS is located at the mitochondrial outer membrane (MOM) in living cells, but in response to pro-apoptotic stimuli it translocates to the cytosol. This permits ARTS to bind and inhibit XIAP, thereby initiating caspase activation and apoptosis. Recently, we have shown that ARTS promotes apoptosis by degrading another major anti-apoptotic protein, BCL-2 (B Cell Lymphoma 2). Many types of cancers express high levels of Bcl-2 and XIAP, contributing to the ability of these cancer cells to avoid cell death and become cancerous. Indeed, both XIAP and BCL-2 have become targets for developing anti-cancer therapies. ARTS is currently the only protein that directly binds and causes degradation of both XIAP and Bcl-2 leading to caspase activation and cell death.
ARTS expression is frequently lost in Acute Lymphoblastic Leukemia (ALL) and in lymphoma patients, indicating that ARTS functions as a tumor-suppressor protein. Furthermore, Sept4/ARTS-null mice exhibit spontaneous tumors and show accelerated tumor development. In addition, Sept4/ARTS-null mice display increased numbers of stem and progenitor cells, which exhibits increased resistance to cell death. Taken together, these results firmly establish the physiological role of ARTS as an XIAP and a novel Bcl-2 antagonist, and a tumor suppressor protein.

Research Status
Prof. Larisch's lab currently focuses on investigating the following:
• Molecular mechanisms of ARTS-induced apoptosis; the multiple signaling pathways by which ARTS promotes apoptosis and necroptosis; the transcriptional regulation of ARTS and its regulation of various other tumor suppressors.
• The role of ARTS as a tumor suppressor in a wide variety of cancer models.
• Characterizing the molecular cell death pathways induced by ARTS small-molecule mimetics.

Carmel established ARTSaVIT ltd, based on Prof. Larisch Research to advance and commercialize this technology, with a seed investment from the Carmel Innovations Fund.

Related pages

ARTSaVIT Ltd

Prof. Sarit Larisch - researcher page

Project name: Medicinal plant extract for treatment of colon cancerProject name: Medicinal plant extract for treatment of colon cancer
Principal researchers name: Prof. Fuad Fares and Dr. Rinat Bar-Shalom
Invention area: Natural Science
Background: Colorectal cancer is the second leading cause of cancer related death in the western world and it is the main cause of mortality among the gastrointestinal cancers in Israel. Approximately 60% of drugs currently in use for cancer treatment have been isolated from natural products and many of them are derived from plants. In the present study we examined the beneficial effects of a medicinal plant extract on colon cancer cells invitro and in vivo.
Results: Treatment with the plant extract demonstrated a profound reduction in cell viability. This reduction was accompanied with inhibition of DNA synthesis, cell cycle arrest at the G2/M phase and induction of apoptosis through both intrinsic and extrinsic pathways. In vivo results indicated that the plant extract has a significant inhibitory effect, which is shown by a deceleration in tumor growth and small final tumor weights and volume. Histological examination clearly revealed apoptotic cells inside the tumor and a decrease in tumor cells' proliferation. No side effects such as weight loss, behavioral changes or changes in kidney and liver functions were observed.
Advantageous:First line treatment for colon cancer is surgery; however the majority of colorectal cancer patients are not candidates for curative local surgery, thus requiring chemotherapy. The effectiveness of chemotherapy treatment has been limited by the side effects and by development of resistance. In order to combat the problem of side effects and chemo-resistance, alternative therapies are required for the treatment of colorectal cancer. Natural products are an important source of anticancer drugs. The medicinal plant extract demonstrated a profound reduction in cell viability in vitro and in tumor progression in vivoand no side effects were observed.
Usage:The importance of this research stems from the profound inhibitory effects of the plant extract on colon cancer cells demonstrated in vitro and in vivo. Therefore, the plant extract is worthy of further investigation in order to be considered as a safe and natural treatment for colon cancer.
 
Carmel Ltd. is looking for potential partners and/or investors in this area. Please  Contact us for further information.