5.2. Therapeutic targeting strategies
Targeting key proteins involved in the regulation of lamellipodia and
filopodia dynamics presents a promising avenue for therapeutic
intervention. Small molecules and inhibitors designed to disrupt the
formation or activity of these cellular protrusions have the potential
to impede cancer cell invasion. Small molecules targeting Rho GTPases,
such as Rac1 and Cdc42, can interfere with the signaling pathways
responsible for lamellipodia and filopodia formation (Table 1 ).
These inhibitors aim to disrupt the cytoskeletal dynamics, inhibiting
the protrusive forces driving cancer cell migration [59–61].
Meanwhile, targeting the WASP-Arp2/3 complex pathway with specific
inhibitors can disrupt the nucleation and branching of actin filaments,
inhibiting lamellipodia formation. Such inhibitors may attenuate the
invasive potential of cancer cells [45]. Therapeutic strategies can
also be designed to target signaling pathways that regulate lamellipodia
and filopodia dynamics. By modulating these pathways, it is possible to
influence the migratory behavior of cancer cells and impede their
invasive capabilities. Small molecules targeting integrins or FAK can
disrupt the signaling cascades that link extracellular signals to the
actin cytoskeleton. This interference may hinder the formation and
stability of lamellipodia and filopodia [62–64]. Developing
inhibitors specific to Ena/VASP proteins could hinder the bundling and
elongation of actin filaments in filopodia. This approach may prove
effective in curtailing the formation and function of filopodia in
cancer cells [65]. Tailoring therapeutic strategies to interfere
with the molecular machinery governing lamellipodia and filopodia
dynamics represents a novel approach in cancer treatment, particularly
for malignancies with a strong invasive component.