Combination of Immunotherapy With Targeted Therapy: Theory and Practice in Metastatic Melanoma

Abstract

Metastatic melanoma is the most aggressive and obstinate skin cancer with poor prognosis. Variant novel applicable regimens have emerged during the past decades intensively, while the most profound approaches are oncogene-targeted therapy and T-lymphocyte mediated immunotherapy. Although targeted therapies generated remarkable and rapid clinical responses in the majority of patients, acquired resistance was developed promptly within months leading to tumor relapse. By contrast, immunotherapies elicited long-term tumor regression. However, the overall response rate was limited. In view of the above, either targeted therapy or immunotherapy cannot elicit durable clinical responses in large range of patients. Interestingly, the advantages and limitations of these regimens happened to be complementary. An increasing number of preclinical studies and clinical trials proved a synergistic antitumor effect with the combination of targeted therapy and immunotherapy, implying a promising prospect for the treatment of metastatic melanoma. In order to achieve a better therapeutic effectiveness and reduce toxicity in patients, great efforts need to be made to illuminate multifaceted interplay between targeted therapy and immunotherapy.

Multiplexed relative and absolute quantitative immunopeptidomics reveals MHC I repertoire alterations induced by CDK4/6 inhibition

“…Indeed, the landscape of clinical trials exploring combination treatment regimens coupling checkpoint blockade with other therapies is rapidly expanding. [53][54][55][56][57] Quantifying the molecular consequences of these combination regimes with our platform could provide novel insights into these trials and enable the informed design of new therapeutic combinations, potentially with targeted immunotherapies. Taken together, our relative and absolute quantitative immunopeptidomic data demonstrate the utility of quantitative immunopeptidomics in evaluating the pMHC repertoire response to therapy.…”

Novel HSP90-PI3K Dual Inhibitor Suppresses Melanoma Cell Proliferation by Interfering with HSP90-EGFR Interaction and Downstream Signaling Pathways

“…Surgical resection is the main therapeutic approach for patients with early melanoma. Given the high malignancy degree of patients with melanoma in advanced stages, the effect of standardized treatment is poor, and the accompanying diagnosis and individualized targeted therapy have become important strategies [1][2][3][4][5][6][7][8]. Several kinase inhibitors, including BRAF inhibitor vemurafenib and dabrafenib, MEK1/2 inhibitor trametinib, c-kit inhibitor imatinib and nilotinib, and other inhibitors targeted to the PI3K/Akt/mTOR signaling pathways, have been approved for the treatment of metastatic melanoma [9][10][11][12][13].…”

Current Insights into Combination Therapies with MAPK Inhibitors and Immune Checkpoint Blockade

“…Despite the benefits of targeted therapies and immunotherapies, they are also associated with a number of limitations. Such limitations may be overcome by combining a targeted therapy and an immunotherapy [3], and several clinical trials investigating combination therapy are ongoing to assess the safety and efficacy of these approaches. Here, we review the current status of therapies targeting the MAPK pathway and immunotherapies, mainly focusing on melanoma and NSCLC, as well as other solid cancers, such as pancreatic cancer, CRC, and thyroid cancer (clinicaltrials.gov).…”