Israeli Scientists Find Mechanism That Causes Cancer Cells to Self-Destruct Hana Levi Julian
Israeli Scientists Find Mechanism That Causes Cancer Cells to Self-Destruct
Israeli scientists have made an enormous discovery that can help lead
to a new treatment for at least two of the most resistant cancers that
exist: pancreatic and triple negative breast cancer.
Many cancer patients struggle with the adverse effects of
chemotherapy, still the most prescribed cancer treatment. For patients
with pancreatic cancer and other aggressive cancers, the forecast is
more grim: there is no known effective therapy.
A new Tel Aviv University study published last month in Oncotarget
discloses the role of three proteins in killing fast-duplicating
cancer cells while they’re dividing. The research, led by Prof. Malka
Cohen-Armon of TAU’s Sackler School of Medicine, finds that these
proteins can be specifically modified during the division process —
mitosis — to unleash an inherent “death mechanism” that
self-eradicates duplicating cancer cells.
“The discovery of an exclusive mechanism that kills cancer cells
without impairing healthy cells, and the fact that this mechanism
works on a variety of rapidly proliferating human cancer cells, is
very exciting,” Prof. Cohen-Armon said. “According to the mechanism we
discovered, the faster cancer cells proliferate, the faster and more
efficiently they will be eradicated. The mechanism unleashed during
mitosis may be suitable for treating aggressive cancers that are
unaffected by traditional chemotherapy.
“Our experiments in cell cultures tested a variety of incurable human
cancer types — breast, lung, ovary, colon, pancreas, blood, brain,”
Prof. Cohen-Armon continued. “This discovery impacts existing cancer
research by identifying a new specific target mechanism that
exclusively and rapidly eradicates cancer cells without damaging
normally proliferating human cells.”
The research was conducted in collaboration with Prof. Shai Izraeli
and Dr. Talia Golan of the Cancer Research Center at Sheba Medical
Center, Tel Hashomer, and Prof. Tamar Peretz, head of the Sharett
Institute of Oncology at Hadassah Medical Center, Ein Kerem.
A new target for cancer research
The newly-discovered mechanism involves the modification of specific
proteins that affect the construction and stability of the spindle,
the microtubular structure that prepares duplicated chromosomes for
segregation into “daughter” cells during cell division.
The researchers found that certain compounds called Phenanthridine
derivatives were able to impair the activity of these proteins, which
can distort the spindle structure and prevent the segregation of
chromosomes. Once the proteins were modified, the cell was prevented
from splitting, and this induced the cell’s rapid self-destruction.
“The mechanism we identified during the mitosis of cancer cells is
specifically targeted by the Phenanthridine derivatives we tested,”
Prof. Cohen-Armon said. “However, a variety of additional drugs that
also modify these specific proteins may now be developed for cancer
cell self-destruction during cell division. The faster the cancer
cells proliferate, the more quickly they are expected to die.”
Research was conducted using both cancer cell cultures and mice
transplanted with human cancer cells. The scientists harnessed
biochemical, molecular biology and imaging technologies to observe the
mechanism in real time. In addition, mice transplanted with triple
negative breast cancer cells, currently resistant to available
therapies, revealed the arrest of tumor growth.
“Identifying the mechanism and showing its relevance in treating
developed tumors opens new avenues for the eradication of rapidly
developing aggressive cancers without damaging healthy tissues,” said
Prof. Cohen-Armon.
The researchers are currently investigating the potential of one of
the Phenanthridine derivatives to treat two aggressive cancers known
to be unresponsive to current chemotherapy: pancreatic cancer and
triple negative breast cancer.
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