Limits...
EGFR-Targeting as a Biological Therapy: Understanding Nimotuzumab's Clinical Effects.

Perez R, Moreno E, Garrido G, Crombet T - Cancers (Basel) (2011)

Bottom Line: Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity.Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile.Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.

View Article: PubMed Central - PubMed

Affiliation: Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba. rolando@cim.sld.cu.

ABSTRACT
Current clinical trials of epidermal growth factor receptor (EGFR)-targeted therapies are mostly guided by a classical approach coming from the cytotoxic paradigm. The predominant view is that the efficacy of EGFR antagonists correlates with skin rash toxicity and induction of objective clinical response. Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity. Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile. Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.

No MeSH data available.


Related in: MedlinePlus

(A). Strategies exploited by tumors to progress and evade the immune response. The picture shows developing tumor cells (orange), cancer stem cells (blue) as well as underlying stroma and nontransformed cells (gray). The different lymphocyte populations are labeled, while the small blue, green and violet, circles represent immune-suppressive factors, chemokines and pro-inflammatory cytokines; (B). Effects of EGFR activation on tumor development; (C). Treatment with an anti-EGFR mAb would induce a biological control of tumor growth and downregulation of the immune-suppressive inflammatory environment. The drawing shows tumor cells arrested in the G0/G1 phase (light orange) and apoptotic cancer stem cells (rough blue), resulting from treatment with Nimotuzumab (violet). For the rest of the elements in the panel, the same labeling scheme and color code as in (a) was applied; (D). Nimotuzumab's mechanisms of action.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3757402&req=5

f2-cancers-03-02014: (A). Strategies exploited by tumors to progress and evade the immune response. The picture shows developing tumor cells (orange), cancer stem cells (blue) as well as underlying stroma and nontransformed cells (gray). The different lymphocyte populations are labeled, while the small blue, green and violet, circles represent immune-suppressive factors, chemokines and pro-inflammatory cytokines; (B). Effects of EGFR activation on tumor development; (C). Treatment with an anti-EGFR mAb would induce a biological control of tumor growth and downregulation of the immune-suppressive inflammatory environment. The drawing shows tumor cells arrested in the G0/G1 phase (light orange) and apoptotic cancer stem cells (rough blue), resulting from treatment with Nimotuzumab (violet). For the rest of the elements in the panel, the same labeling scheme and color code as in (a) was applied; (D). Nimotuzumab's mechanisms of action.

Mentions: Different pieces of experimental and modeling data, gathered in recent years, support four complementary mechanisms to explain the low degree of adverse effects and the long-term disease stabilizations observed for Nimotuzumab in the clinic (Figure 2).


EGFR-Targeting as a Biological Therapy: Understanding Nimotuzumab's Clinical Effects.

Perez R, Moreno E, Garrido G, Crombet T - Cancers (Basel) (2011)

(A). Strategies exploited by tumors to progress and evade the immune response. The picture shows developing tumor cells (orange), cancer stem cells (blue) as well as underlying stroma and nontransformed cells (gray). The different lymphocyte populations are labeled, while the small blue, green and violet, circles represent immune-suppressive factors, chemokines and pro-inflammatory cytokines; (B). Effects of EGFR activation on tumor development; (C). Treatment with an anti-EGFR mAb would induce a biological control of tumor growth and downregulation of the immune-suppressive inflammatory environment. The drawing shows tumor cells arrested in the G0/G1 phase (light orange) and apoptotic cancer stem cells (rough blue), resulting from treatment with Nimotuzumab (violet). For the rest of the elements in the panel, the same labeling scheme and color code as in (a) was applied; (D). Nimotuzumab's mechanisms of action.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757402&req=5

f2-cancers-03-02014: (A). Strategies exploited by tumors to progress and evade the immune response. The picture shows developing tumor cells (orange), cancer stem cells (blue) as well as underlying stroma and nontransformed cells (gray). The different lymphocyte populations are labeled, while the small blue, green and violet, circles represent immune-suppressive factors, chemokines and pro-inflammatory cytokines; (B). Effects of EGFR activation on tumor development; (C). Treatment with an anti-EGFR mAb would induce a biological control of tumor growth and downregulation of the immune-suppressive inflammatory environment. The drawing shows tumor cells arrested in the G0/G1 phase (light orange) and apoptotic cancer stem cells (rough blue), resulting from treatment with Nimotuzumab (violet). For the rest of the elements in the panel, the same labeling scheme and color code as in (a) was applied; (D). Nimotuzumab's mechanisms of action.
Mentions: Different pieces of experimental and modeling data, gathered in recent years, support four complementary mechanisms to explain the low degree of adverse effects and the long-term disease stabilizations observed for Nimotuzumab in the clinic (Figure 2).

Bottom Line: Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity.Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile.Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.

View Article: PubMed Central - PubMed

Affiliation: Center of Molecular Immunology, P.O. Box 16040, Havana 11600, Cuba. rolando@cim.sld.cu.

ABSTRACT
Current clinical trials of epidermal growth factor receptor (EGFR)-targeted therapies are mostly guided by a classical approach coming from the cytotoxic paradigm. The predominant view is that the efficacy of EGFR antagonists correlates with skin rash toxicity and induction of objective clinical response. Clinical benefit from EGFR-targeted therapies is well documented; however, chronic use in advanced cancer patients has been limited due to cumulative and chemotherapy-enhanced toxicity. Here we analyze different pieces of data from mechanistic and clinical studies with the anti-EGFR monoclonal antibody Nimotuzumab, which provides several clues to understand how this antibody may induce a biological control of tumor growth while keeping a low toxicity profile. Based on these results and the current state of the art on EGFR-targeted therapies, we discuss the need to evaluate new therapeutic approaches using anti-EGFR agents, which would have the potential of transforming advanced cancer into a long-term controlled chronic disease.

No MeSH data available.


Related in: MedlinePlus