RT Journal Article
SR Electronic
T1 Integrating Immunotherapy and Targeted Therapy in Cancer Treatment: Mechanistic Insights and Clinical Implications
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 5557
OP 5566
DO 10.1158/1078-0432.CCR-19-2300
VO 26
IS 21
A1 Bergholz, Johann S.
A1 Wang, Qiwei
A1 Kabraji, Sheheryar
A1 Zhao, Jean J.
YR 2020
UL http://clincancerres.aacrjournals.org/content/26/21/5557.abstract
AB Small-molecule targeted therapies have demonstrated outstanding potential in the clinic. These drugs are designed to minimize adverse effects by selectively attacking cancer cells while exerting minimal damage to normal cells. Although initial response to targeted therapies may be high, yielding positive response rates and often improving survival for an important percentage of patients, resistance often limits long-term effectiveness. On the other hand, immunotherapy has demonstrated durable results, yet for a limited number of patients. Growing evidence indicates that some targeted agents can modulate different components of the antitumor immune response. These include immune sensitization by inhibiting tumor cell–intrinsic immune evasion programs or enhancing antigenicity, as well as direct effects on immune effector and immunosuppressive cells. The combination of these two approaches, therefore, has the potential to result in synergistic and durable outcomes for patients. In this review, we focus on the latest advances on integrating immunotherapy with small-molecule targeted inhibitors. In particular, we discuss how specific oncogenic events differentially affect immune response, and the implications of these findings on the rational design of effective combinations of immunotherapy and targeted therapies.