New Treatment on the horizon

[Schallen]

TASIN Selectively Targets Colon Cancer Cells Expressing Truncated APC


A study conducted at the Departments of Biochemistry (Jef De Brabander)
and Cell Biology (Jerry Shay), University of Texas Southwestern Medical
Center, Dallas, TX has demonstrated that TASIN (Truncated APC Selective
INhibitor), a recently identified small molecule, selectively kills
colorectal cancer cells (CRC) by inducing endoplasmic reticulum (ER)
stress which leads to activation of the pro-apoptotic JNK pathway and
PARP cleavage. The ER is a central organelle involved in protein
folding, protein maturation and lipid synthesis. Interference in ER
homeostasis, results in an accumulation of misfolded or unfolded
proteins in the ER lumen. In addition, TASIN inhibits pro-survival, AKT
activity through a cholesterol-dependent manner in CRC cells. The
research was published in the journal Molecular Cancer Therapeutics (Mol
Cancer Ther. 2018 Feb 21. pii: molcanther.0887.2017. doi:
10.1158/1535-7163.MCT-17-0887. [Epub ahead of print]).

Mutation of the APC tumor suppressor gene is a frequent and early, if
not initiating, event in CRC tumorigenesis, and present in about 80% of
all CRC tumors. TASIN induces ER stress and oxidative stress due to
intracellular cholesterol depletion, specific to truncated
APC-expressing cells.

"Our results reveal the downstream mechanism which drives TASIN induced
apoptotic cell death in truncated APC cells. This knowledge could aid in
the future clinical development of TASIN as a novel targeted therapeutic
strategy for colorectal cancer patients." said Jerry W. Shay, senior
author of the study, and professor of Cell Biology at UT Southwestern
Medical Center.

TASIN had previously been shown to have synthetic lethality in CRC cells
expressing truncated APC, while sparing normal cells expressing
wild-type APC. The compound induces cell death through depletion of
cholesterol in truncated APC cells. However, the downstream mechanism in
response to TASIN induced cholesterol depletion were unknown prior to
these studies.

"TASIN is a fascinating innovative drug candidate that selectively kills
colon cancer cells without harming healthy cells, and it may be the
first truly targeted compound for CRC," said Frank Perabo, CEO of
Barricade. "These data expand our understanding and knowledge around the
mode of action of TASIN and support our efforts to advance this compound
to clinical trials."


https://www.benzinga.com/pressreleases/ ... ncated-apc

[Shana]

Thank you for sharing, very interesting research happening across the country.

What is your connection to CRC? Are you a patient or caregiver?