Highlights•Optimal drug combinations require understanding of the drug-induced changes
in cellular states.•The dynamics of signaling molecules can be reporters for cellular states …

The majority of diseases are associated with alterations in multiple molecular pathways and
complex interactions at the cellular and organ levels. Single-target monotherapies therefore …

Numerous practical issues must be considered when combining targeted therapies in early
clinical drug development. These include tumor resistance mechanisms, the existence of …

We are witnessing several revolutionary technological advances in cancer. These
innovations have not only contributed to a growing understanding of the tumor and its …

Cancer therapies that target key molecules have not fulfilled expected promises for most
common malignancies. Major challenges include the incomplete understanding and …

Background Anticancer therapies that target single signal transduction pathways often fail to
prevent proliferation of cancer cells because of overlapping functions and cross-talk …

Combinatorial control of biological processes, in which redundancy and multifunctionality
are the norm, fundamentally limits the therapeutic index that can be achieved by even the …

During evolution, connections between the major signalling pathways were established to
provide cells with an ability to deal with perturbations of homeostasis. However, these …

Disseminated cancer remains a largely fatal disease. While systemic therapy can have
some initial success, it is rarely durable. Typically, populations of cancer cells resistant to …

Signaling networks are nonlinear and complex, involving a large ensemble of dynamic
interaction states that fluctuate in space and time. However, therapeutic strategies, such as …