2017, Number 4
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Rev Esp Med Quir 2017; 22 (4)
Molecular biology of cancer and new tools in oncology
Pérez-Cabeza de Vaca R, Cárdenas-Cárdenas E, Mondragón-Terán P, Erazo-Valle Solís AA
Language: Spanish
References: 45
Page: 171-181
PDF size: 1306.16 Kb.
ABSTRACT
Cancer is not defined as a single disease, but a heterogeneous
group of diseases, characterized by the accumulation of mutations
in the genome of cells, to the point where these mutations affect
the various functions at the molecular, cellular, tissue, and systemic
levels, with the consequent death of the patient. Hanahan and
Weinberg described the hallmarks or features of cancer, such as the
cancer cell’s capacity for development and progression of clinically
manifest cancer. The six traits are to maintain proliferative signaling,
to avoid suppression of growth, to resist cell death, to activate invasion
and metastasis, to allow replicative immortality and to induce
angiogenesis; energy deregulation, immune response evasion, inflammation
and genetic instability can also be considered. These
features are targets of multiple investigations in order to molecularly
characterize cancer and develop new therapeutic tools specifically
directed against the cellular mechanisms and signaling pathways
that are altered in that pathology. Within the deregulated
mechanisms in tumor cells, we generally find that these cells are
rapidly duplicating and that their rate of proliferation is greater than
that of normal tissue of origin, this mainly because their cell cycle
and its regulatory points are deregulated, activating oncogenes and
extinguishing tumor suppressor genes. This deregulation allows the
escape of tumor cells from their normal cell cycle, promoting the
invasion of blood vessels that nourish the tumor by angiogenesis
and even allows these cells to circulate and invade other tissues or
organs in the process known as metastasis. In the last 50 years
medical oncology has witnessed a revolution thanks to the therapies
directed against these specific molecular targets that have been
identified in the different neoplasias. Mutations of
BRCA1/2 in
breast and ovarian cancer, mutations in MMR (mis-match-repair),
RAS and
BRAF in colon and rectum cancer, mutations in
RAS, BRAF,
ALK, ROS and
MET in lung cancer, mutations in
BRAF and
KIT in
melanoma and in tumors of the gastrointestinal stromal. Mutations
in KIT are some of the genetic alterations that nowadays are
looked for perhaps routine form in medical practice. Advances in
molecular biology have not only allowed a better understanding
of the molecular pathophysiology of cancer, but also the use of
novel therapies such as monoclonal antibodies, such as cetuximab
and panitumumab, sorafenib, olaparib for mutations in oncogenes
and tumor suppressor genes that are deregulated or as sunitinib and
pazopanib, which are other inhibitors of tyrosine kinase with activity
in different signaling pathways, trastuzumab and pertuzumab as
monoclonal antibodies against the vascular endothelial growth receptor,
among others, thus impacting on the favorable increase in
the life expectancy of cancer patients and the possibilities of their
treatment.
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