Related Experiment Video
Updated: Jul 13, 2026
A Data Integration Workflow to Identify Drug Combinations Targeting Synthetic Lethal Interactions
Published on: May 27, 2021
The lethal phenotype of cancer: the molecular basis of death due to malignancy
Robert D Loberg1, Deborah A Bradley, Scott A Tomlins
1Internal Medicine and Urology, University of Michigan, Ann Arbor, MI, USA.
Abstract:
The last decade has seen an explosion in knowledge of the molecular basis and treatment of cancer. The molecular events that define the lethal phenotype of various cancers--the genetic and cellular alterations that lead to a cancer with a poor or incurable prognosis--are being defined. While these studies describe the cellular events of the lethal phenotype of cancer in detail, how these events result in the common clinical syndromes that kill the majority of cancer patients is not well understood. It is clear that the central step that makes most cancers incurable is metastasis. Understanding the traits that a cancer acquires to successfully grow and metastasize to distant sites gives insight into how tumors produce multiple factors that result in multiple different clinical syndromes that are lethal for the patient.
Insights
Cancer
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Recent advances have significantly increased understanding of the molecular basis and treatment of cancer.
- Molecular events defining lethal cancer phenotypes (genetic/cellular alterations leading to poor prognosis) are being elucidated.
- However, the link between these cellular events and the clinical syndromes causing cancer mortality remains poorly understood.
Purpose of the Study:
- To bridge the knowledge gap between the molecular events of lethal cancer phenotypes and their resulting clinical manifestations.
- To investigate how cancer's lethal phenotype contributes to the development of fatal clinical syndromes.
- To highlight the critical role of metastasis in cancer incurability and patient mortality.
Main Methods:
- Review and synthesis of current research on cancer molecular biology and lethal phenotypes.
- Analysis of the relationship between cellular alterations and clinical syndromes in advanced cancers.
- Focus on the process of metastasis as a key determinant of cancer lethality.
Main Results:
- Metastasis is identified as the central mechanism rendering most cancers incurable.
- Understanding cancer traits for growth and metastasis provides insight into lethal clinical syndromes.
- Tumors produce multiple factors contributing to diverse and fatal clinical outcomes.
Conclusions:
- Elucidating the molecular basis of metastasis is crucial for understanding and treating lethal cancer.
- Connecting molecular cancer phenotypes to clinical syndromes is essential for improving patient outcomes.
- Further research into tumor-derived factors driving metastasis and clinical syndromes is warranted.
Related Concept Videos
02:41Lethal Alleles
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:05Cancer-Critical Genes II: Tumor Suppressor Genes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:30Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...