The Phenotype Landscape of Cancer in the Genotype Era.
Some tumor types such as testicular cancer, leukemia and lymphomas, have their origin in cells that comport a common embryonic origin. This phenomenon was “unconsciously” the roadmap to treat and cure them by classic chemotherapy.
Chemotherapy has also positively impacted the overall survival of some pediatric and adolescent cancers and in many other adult ones such as breast, ovarian, head and neck and colorectal cancers. Despite everything, we also face other difficult to treat cancers which remain chemo resistant.
As basic and translational cancer researches evolve, these tumor-types have turned into a significant focal point of intrigue. So, what to do in order to work-out this cancer resistance dilemma? Targeting some tumor genetic mutations such as those of the tyrosine kinase types, oncogene- driven growth factor receptors and some immune molecules such as those of the programmed-death pathway and the cytotoxic T-lymphocyte-associated protein 4 axis, enable us to battle the malignant growth.
Regarding these aforementioned cellular pathways, drugs which are of small molecules, target the first two druggable ones and treat lung, renal and malignant melanoma. The third one, “the mammoths”: monoclonal antibodies, can disrupt angiogenic pathways, block some oncogenic drivers and mainly deblock the lazy T-lymphocytes by allowing them to eat tumors.
This last one, became the treatment of cancer by the inhibition of negative immune regulation for which the researchers have been granted Nobel prize. The answer for therapy failures is related to the old concept of tumor heterogeneity.
Tumor cell phenotype heterogeneity is the main cause of secondary resistance and also of progression in the already mentioned chemo sensitive tumors, and one of the main causes of the non-tumor responses in the less de novo chemo sensitive.