Mitosis-targeted anti-cancer therapies: where they stand. K-S Chan, C-G Koh and H-Y Li
The strategy of clinically targeting cancerous cells at their most vulnerable state during
mitosis has instigated numerous studies into the mitotic cell death (MCD) pathway. As cancer is
caused by cell-cycle deregulation, it is not surprising that antimitotic therapies are effective
against the abnormal increase of transformed cells. Moreover, these antimitotic drugs are also
highly selective and sensitive. Despite the robust rate of discovery and the development of
mitosis-selective inhibitors, the unpredictable complexities of the human body’s response to
these drugs still herald the biggest challenge towards clinical success.
With a long history of clinical efficacy, microtubule-targeting agents (MTAs) are
reliably effective. These drugs disrupt proper microtubule dynamics, leading to abnormal spindle
formation, chromosome misalignment and the perpetual activation of SAC. MTAs are active in a
wide range of tumors, particularly breast, ovarian, non-small-cell-lung and head-and-neck
cancers.
Definitions
MTA— microtubule-targeting agents. Chemotherapy drugs that specifically target the mitotic
cycle in order to kill cancerous cells.
SAC—spindle assembly checkpoint. Stops mitosis, usually leads to cell death.
Polymerization drugs—prevent spindle fibers from retracting/dissolving after mitosis. Interrupt
the mitotic cycle.
Depolymerization drugs—prevent spindle fibers from forming properly, interrupt the cell cycle.
Metastasis: from dissemination to organ-specific colonization. Don Nguyen, Paula D. Bos
and Joan Massagué
Metastasis to distant organs is an ominous feature of most malignant tumors but the
natural history of this process varies in different cancers. The cellular origin, intrinsic properties
of the tumor, tissue affinities and circulation patterns determine not only the sites of tumor
spread, but also the temporal course and severity of metastasis to vital organs.
At a glance
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Metastasis progression can be viewed as a stepwise sequence of events, which is
mediated by the different classes of metastasis genes.
For each type of cancer, the clinical course of these events occurs with distinct
temporal kinetics and in unique organ sites.
The long latency period of certain tumor types suggests the further evolution or
‘speciation’ of malignant cells in the microenvironments of a particular organ. The
acquisition of pro-metastatic functions earlier during primary tumor formation might
enable other cancer types to relapse more quickly
The organ specificity of metastatic cells is determined by unique infiltrative and
colonization functions required after their dissemination from a primary tumor.
Definitions
Metastasis—the spread of cancer from one affected organ, to a different organ.
Latency period—the time period between infection, and when signs and symptoms begin.
Apoptosis: Its Significance in Cancer and Cancer Therapy John Kerr, Clay Winterford, Brian
V. Harmon
Oncologists traditionally have been concerned primarily with cell proliferation. However,
apoptosis (the distinctive form of cell death that complements cell proliferation in normal tissue
homeostasis) increasingly has been attracting their attention. In particular, the discovery that
apoptosis can be regulated by the products of certain proto-oncogenes and the p53 tumor
suppressor has opened up exciting avenues for future research.
The proposition that apoptosis is a discrete phenomenon that is fundamentally different
from degenerative cell death or necrosis is based on its morphology, biochemistry, and incidence.
Apoptotic bodies arising in tissues are quickly ingested by nearby cells and degraded within their
lysosomes (Fig. 6). There is no associated inflammation with the outpouring of specialized
phagocytes into the tissue, such as occurs with necrosis, and various types of resident cells,
including epithelial cells (Fig. 6), participate in the mopping-up process. In tumors, viable
neoplastic cells usually are involved, as are resident macrophages. However, apoptotic bodies
formed in cell cultures mostly escape phagocytosis and eventually degenerate.
Scitable – Nature Education.
Cancer cells are cells gone wrong — in other words, they no longer respond to many of the
signals that control cellular growth and death. Cancer cells originate within tissues and, as they
grow and divide, they diverge ever further from normalcy. Over time, these cells become
increasingly resistant to the controls that maintain normal tissue — and as a result, they divide
more rapidly than their progenitors and become less dependent on signals from other cells.
Cancer cells even evade programmed cell death, despite the fact that their multiple abnormalities
would normally make them prime targets for apoptosis. In the late stages of cancer, cells break
through normal tissue boundaries and metastasize (spread) to new sites in the body.
How Do Cancer Cells Differ from Normal Cells?
In normal cells, hundreds of genes intricately control the process of cell division. Normal growth
requires a balance between the activity of those genes that promote cell proliferation and those
that suppress it. It also relies on the activities of genes that signal when damaged cells should
undergo apoptosis.
Cells become cancerous after mutations accumulate in the various genes that control cell
proliferation. According to research findings from the Cancer Genome Project, most cancer cells
possess 60 or more mutations. The challenge for medical researchers is to identify which of these
mutations are responsible for particular kinds of cancer. This process is akin to searching for the
proverbial needle in a haystack, because many of the mutations present in these cells have little
to nothing to do with cancer growth.