J Pharm Pharmacogn Res 2(Suppl. 1): S98, 2014

Special supplement with the abstract book of LATINFARMA 2013



Soriano García JL.

Clinical Oncology Service. Ameijeiras´Hospital, La Habana, Cuba.

Cancer therapy is designed to specifically integrate distinct treatment modalities in the most effective way to achieve the highest cure rate. Surgery and radiation therapies are used for loco regional disease control, whereas systemic therapies are used to treat micrometastatic or widespread metastatic cancers and hematologic malignancies. While systemic therapies have historically been given after local measures have been undertaken to remove the primary tumor, they are increasingly used prior to definitive local treatment both to achieve systemic disease control earlier and to evaluate the responsiveness of the tumor to treatment. Regardless of the timing in relation to local therapy, these systemic treatments—chemotherapy, endocrine therapy, small molecular targeted therapies and monoclonal antibodies–are designed to decrease the likelihood of relapse due to micrometastatic disease. Cancer chemotherapy drugs have long been considered immune suppressive. However, more recent data indicate that some cytotoxic drugs effectively treat cancer in part by facilitating an immune response to the tumor when given at the standard dose and schedule. These drugs induce a form of tumor cell death that is immunologically active, thereby inducing an adaptive immune response specific for the tumor. In addition, cancer chemotherapy drugs can promote tumor immunity through ancillary and largely unappreciated immunologic effects on both the malignant and normal host cells present within the tumor microenvironment. These more subtle immunomodulatory effects are dependent on the drug itself, its dose, and its schedule in relation to an immune-based intervention. A detailed understanding of the cellular and molecular basis of interactions between chemotherapy drugs and the immune system is essential for devising the optimal strategy for integrating new immunebased therapies into the standard of care for various cancers, resulting in the greatest long-term clinical benefit for cancer patients. Current data suggest that combining chemotherapy in standard and novel ways with immune-based interventions will have great potential for optimizing the clinical outcomes of cancer patients. A new era of effectively harnessing the immune system to treat and prevent cancer has begun. These early successes have ledto heightened interest and activity in developing new strategies for tipping the balance of the hosttumor interaction toward definitive tumor rejection. It is clear that strategically integrating immune-based therapies with standard cancer treatment modalities, in particular chemotherapy drugs, has the potential to reengineer the overall host milieu and the local tumor microenvironment to disrupt pathways of immune tolerance and suppression (to understand the differences in immunobiology between the distinct histologies and biologic subtypes of cancer will be critical for identifying the optimal antigen and/or immunologic pathway to target for a particular cancer or to dissect mechanisms of intrinsic and adaptive therapeutic resistance to immune-based treatments will be critical for ensuring clinical success). In designing combination immunotherapy regimens, clinical investigators should consider how chemotherapy impacts the immune system in order to guide the dose and schedule for integrating chemotherapy and immunotherapy. In particular, systematically defining the optimal drug dose and timing in relation to immune-based therapy in early-phase clinical studies is imperative for the design of phase II and III clinical trials with a higher
likelihood of clinical success. Finally, delineating the impact of established cancer drugs and standard cancer treatment modalities on the immune system and on tumor immuno biology itself will be critical for the most effective integration of immune-based cancer therapy into state-of-the art multimodality cancer care.