The Evolving Landscape of Cancer Therapeutics

Inhaled cytotoxic chemotherapy: clinical challenges, recent developments, and future prospects

“…Moreover, tumors are organized as complex tissues that include a microenvironment favorable to their survival [25]. As cancer presents proliferative and invasive properties with the ability to resist regulatory systems such as the immune system and to adapt to their environment, different modalities are used and combined to treat it [26]. These modalities are surgery and radiotherapy as localized treatments and chemotherapy (i.e.…”

“…cytotoxic chemotherapy), targeted therapy, hormonotherapy, and immunotherapy as systemic treatments. They are applied and combined according to the histology of cancer, the stage of the disease and the molecular characteristics of cancer cells as well as the performance status of the patient [26]. Cytotoxic chemotherapy is used at almost all stages of the disease to combat the risk of invasion (i.e.…”

“…These systemic routes of administration distribute the cytotoxic drugs to all parts of the body before reaching the tumor. They therefore inevitably cause severe systemic and dose-limiting toxicities (DLTs) to the patient due to their dose-dependent pharmacological effects [26,28]. Such poorly selective cytotoxic chemotherapies therefore affect rapidly-dividing tissues such as not only tumors but also bone marrow, gastrointestinal mucosa, skin, and gonads.…”

“…Such poorly selective cytotoxic chemotherapies therefore affect rapidly-dividing tissues such as not only tumors but also bone marrow, gastrointestinal mucosa, skin, and gonads. Therefore, these therapies very often induce myelosuppression, nauseas and vomiting, alopecia, and infertility (for women), respectively [26]. Some toxicities are more organspecific, such as nephrotoxicity for CIS, neurotoxicity for paclitaxel, or cardiotoxicity for doxorubicin [28].…”

“…Moreover, conventional drugs are mostly used in association, leading to higher efficacy but also to accumulation and/or aggravation of adverse effects, requiring dose adaptations [29,30]. As these toxicities strongly limit the delivered dose, the plasma concentrations are often not high enough to be completely therapeutically effective at the tumor site [26]. This point is crucial.…”