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Seminar

Thursday, 20th, June 2024
10h
Centre de recherche - Paris - Amphithéâtre Hélène Martel-Massignac (BDD)

Lineage- and species-specific sensitivity or resistance to cancer - Insights from RB loss and KRAS activation

It is known but poorly understood why the common effect of “oncogenic” mutations is not cancer.  Lineages that are cancer-prone are far outweighed by those that are cancer-resistant.  On another level, cancer susceptibility of orthologous lineages is also species-specific. For example, human RB null cone photoreceptor precursors are cancer-prone, but cancer resistant in other mammals.  We have deduced the underlying molecular network explaining this difference, generating the first cone-derived murine model of retinoblastoma.  As well as species specificity, RB mutation also provides striking examples of lineage specific susceptibility to transformation. Why one lineage is cancer-prone and another cancer resistant is unknown.  We uncovered a hallmark of lineage-specific susceptibility to RB loss. Remarkably, a tissue can exhibit numerous hallmarks of mature cancer, but if the initiation hallmark is not present, the tissue remains cancer-free. In lung, RB loss or KRAS activation render distinct lineages cancer-prone.  Our cancer initiation hallmark predicts the cancer-prone lineage in both scenarios.  Together our work provides insight into species and lineage specific resistance or susceptibility to neoplastic transformation, raising new strategies for therapeutic intervention.

Event poster

Speaker(s)

Rod BREMNER

Lunenfeld Tanenbaum Research Institute, Canada

Invited by

Francois RADVANYI
Biologie cellulaire et Cancer (UMR144)

Institut Curie

Pierre LEOPOLD
Génétique et biologie du développement (UMR3215 / U934)

Institut Curie

Contact

Francois RADVANYI

Institut Curie

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