Combination Therapies: Balancing Efficacy and Adverse Events

Cancer is one of the leading causes of death worldwide and is characterized by the unregulated proliferation of mutated cells, tumor development, and, in many cases, metastasis to distant sites. Cancer treatment is often difficult because pre-existing mutations and genetic instability allow malignant cells to accumulate additional mutations, evade normal regulatory signals, and develop resistance to therapy. Common treatments, including chemotherapy, small-molecule inhibitors, monoclonal antibodies, and immunotherapies, target cancer cells through different mechanisms and may be used alone or in combination to reduce tumor size and prevent further proliferation. However, many of these treatments can cause unwanted side effects because of systemic cytotoxicity, off-target effects, or immune-related toxicity, leading to ongoing efforts to improve treatment efficacy while reducing harm to patients. Combination therapies, including antibody-drug conjugates, targeted therapies combined with chemotherapy, and targeted therapies combined with immunotherapy, aim to target multiple proteins or pathways, enhance antitumor immune responses, reduce resistance, limit immune suppression, and prevent further proliferation and metastasis. Although these approaches can improve survival outcomes and reduce tumor burden more effectively in some cancers, they may also cause more severe side effects due to overlapping toxicities. This review explores different combinations of targeted therapies and immunotherapies to evaluate their effectiveness while also assessing their potential drawbacks related to adverse effects.