Combination Therapy as a Promising Way to Fight Oral Cancer
Abstract
:1. Introduction
2. Current Therapeutic Options for Oral Cancer Treatment
Therapies | Advantages | Disadvantages | References |
---|---|---|---|
Surgery |
|
| [29,30] |
Radiotherapy |
|
| [30,31,32] |
Chemotherapy |
|
| [30,33] |
3. New Combinatorial Approaches for Oral Cancer Treatment
3.1. DNA Damage Response Inhibition-Based Combination Therapies
Combination Therapies | Study Design/Treatment Type | Cancer Type and Stage | Main Reported Outcome | References |
---|---|---|---|---|
PLA nanoparticles loaded with Cisplatin–chloroquine | Preclinical trials | N/A | Inhibited OSCC proliferation through oxidative stress and apoptosis. | [39,40] |
Transfersomes loaded with 5-FU and COX-2 inhibitors | Preclinical trial | N/A | Exerted synergistic effects, increasing drug delivery efficiency. | [44] |
Cisplatin plus Gemcitabine and Rituximab | Phase 1 clinical trial Patients previously treated | - R/M HNSCC | The treatment was considered safe, but no clinical benefit could be ascertained. | [89] |
Cisplatin with a PARP inhibitor | Preclinical trial | N/A | Exerted synergistic effects in vitro and potentiated in vivo tumor growth suppression. | [47] |
Combination of a PARP inhibitor with Cisplatin and Paclitaxel | Phase 1 clinical trial 1st line (IC) | LA-HNSCC IVA-B | Displayed low toxicity and was well tolerated. | [48] |
PARP inhibitors combined with Curcumin | Preclinical trials | N/A | Enhanced anti-angiogenic activity and increased cell death. | [50,51] |
ATO combined with Cisplatin | Preclinical trial | N/A | Exerted synergistic effects, increasing OSCC apoptosis. | [56] |
Gimeracil combined with Cisplatin | Preclinical trial | N/A | Inhibited in vitro and in vivo OSCC tumor growth | [64] |
Combination of 5-FU with Juniperus communis extract | Preclinical trial | N/A | Exerted synergistic effects, potentiating proliferative inhibition. | [65] |
Azurin combined with 5-FU or Etoposide | Preclinical trial | N/A | Increased OSCC sensibility, improving anticancer response. | [66] |
Propofol combined with 5-FU | Preclinical trial | N/A | Reduced pharmacological resistance of oral cancer cells. | [70] |
Combination of Cisplatin with PI3K/AKT/mTOR pathway inhibitors and radiotherapy | Phase 1 clinical trials - | LA-HNSCC ≥III | Exhibited satisfactory OS and PFS rates. | [76,77] |
Combination of S-1 with Bevacizumab | Preclinical trial | N/A | Exerted synergistic effects, causing in vitro cell proliferation inhibition, and exacerbated apoptosis in vivo. | [83] |
Combination of 5-FU with Bevacizumab | Preclinical trial | N/A | Exerted no synergistic effects, but was able to reduce cell proliferation. | [83] |
Bevacizumab combined with Cisplatin and Gemcitabine | Phase 2 clinical trial - | LA NPC III–IVc | Displayed anticancer activity and was well tolerated. | [84] |
Xevinapant, Cisplatin, and radiotherapy | Phase 1/2 clinical trials - | LA-HNSCC III/IVa/IVb | Showed improved efficacy. A 5-year follow-up demonstrated improved 5-year OS and 3-year PFS, and was deemed safe. | [90,91] |
Dichloroacetate, Cisplatin, and radiotherapy | Phase 2 clinical trial 1st line | LA-HNSCC III/IVa/IVb | The treatment was safe, but the efficacy could not be determined. | [92] |
Gemcitabine in combination with Nedaplatin and radiotherapy | Clinical trial - | R/M or LA-HNSCC III–IV | Can be a therapeutic option for HNSCC, although high number of adverse events highlights the need for the optimization of dose and schedule. | [93] |
Combination of Bortezomib, Camptothecin, and Doxorubicin | Preclinical trial | N/A | Potentiated cytotoxicity only in KB oral cancer cells and not in non-cancerous cells. | [94] |
Postoperative weekly administration of Cisplatin plus radiation | Phase 2/3 clinical trial Postoperative | LA-HNSCC III/IVa/IVb | Similar efficacy, but less toxicity when compared with 3-weekly Cisplatin administration. | [95] |
One cycle chemoselection split-dose TPF IC before two cycles of split TPF followed by curative surgery combined with postoperative radiotherapy | Phase 2 clinical trial - | LA OPSCC and LA OCC III/IVa | Well tolerated and a good strategy to select patients that will benefit with TPF treatment. | [96] |
TPF as induction chemotherapy | Phase III clinical trial 1st line (IC) | LA OSCC - | Did not improve survival of unselected patients, but patients which achieved FPR had good OS and PFS. | [97] |
3.2. Epidermal Growth Factor Receptor Inhibition-Based Combination Therapies
Combination Therapies | Study Design/ Treatment Type | Cancer Type and Stage | Main Reported Outcome | References |
---|---|---|---|---|
EGFR inhibition combined with radiotherapy | Phase 3 clinical trial - | LA-HNSCC III/IV | Exerted supra-additive effects, increasing OS. | [121] |
Retrospective study 1st and 2nd lines | OCSCC ≥I | Slightly less effective than when assessed for HNSCC patients, but deemed safe and with good efficacy. | [122] | |
Combination of EGFR and PI3K inhibitors | Phase 2 clinical trial 2nd and 3rd lines | R/M HNSCC II/III/IV | Exhibited no improvement of PFS, ORR, and OS. | [128] |
Phase 1 clinical trial Most patients previously treated | R/M HNSCC - | Associated with high toxicity and poor efficacy. | [129] | |
Alpelisib combined with Cetuximab and IMRT | Phase 1b clinical trial - | LA-HNSCC III/IVa/IVb | This treatment modality was considered safe. | [131] |
Combination of EGFR inhibitors with drugs that target DNA repair defective tumors | Preclinical trial | N/A | Improved cytotoxicity and increased in vitro and in vivo radiation effects. | [135] |
EGFR mAb combined with pan-aurora inhibitors | Preclinical trial | N/A | Exerted additive effects in inhibiting cell growth. | [138] |
Combination of HER-3 and EGFR inhibitors | Preclinical trial | N/A | Enhanced the suppression of cell proliferation in vitro and in vivo. | [106] |
Phase 1/1b clinical trials Most patients previously treated | R/M HNSCC - | Showed great anticancer activity and was well tolerated. | [130,146] | |
Patritumab combined with Cetuximab and platinum | Phase 2 clinical trial 1st line | R/M HNSCC III/IVa-c | Exhibited good tolerability, but did not improve combination of Cetuximab and platinum. | [147] |
Combination of EGFR and ERK inhibitors | Preclinical trial | N/A | Exerted synergistic effects, enhancing anticancer activity. | [148] |
Phase 1b clinical trial Patients previously treated | SGC - | Exerted no synergistic effects with limited efficacy and poor tolerability. | [149] | |
Combination of EGFR and c-Met inhibitors | Preclinical trial | N/A | Enhanced anticancer efficacy in in vitro and in vivo models. | [5] |
Phase 2 clinical trial ≥1st line | R/M HNSCC - | Displayed high toxicity associated with no improvement in tumor response or OS. | [152] | |
Combination of EGFR and VEGF inhibitors | Preclinical and phase 2 clinical trial Patients previously treated | R/M HNSCC - | Delayed tumor growth and inhibited tumor angiogenesis in vitro and in vivo. Deemed safe and showed activity in previously treated patients. | [155] |
Cetuximab combined with Pazopanib | Phase 1b clinical trial ≥1st line | R/M HNSCC - | Showed safety and a good antitumor response. | [158] |
Cetuximab combined with Sorafenib | Phase 2 clinical trial - | R/M HNSCC - | Exerted no significant survival response and showed high toxicity when compared to Cetuximab monotherapy. | [153] |
Combination of Cetuximab, Bevacizumab, and Temsirolimus | Phase 1 clinical trial Mostly patients previously treated | HNSCC - | Exhibited good anticancer response; however, high toxicity was observed. | [161] |
Combined Cetuximab and Temsirolimus | Phase 2 clinical trial R/M HNSCC | - - | Did not improve PFS, but induced response in Cetuximab refractory patients with good safety profile. | [162] |
Everolimus in combination with Erlotinib | Phase 2 clinical trial Patients previously treated and untreated | R/M HNSCC - | Was deemed safe, but no benefit was observed for this combination. | [163] |
Bevacizumab combined with platinum-based chemotherapy | Phase 3 clinical trial Patients previously treated and untreated | R/M HNSCC - | Exhibited no significant OS improvement and increased toxicity. Nonetheless, PFS and ORR improved. | [164] |
Bevacizumab in combination with Cisplatin and IMRT | Phase 2 clinical trial 1st line | LA-HNSCC III/IVa/IVb | Slightly increased toxicity and promising efficacy were observed. | [165] |
Combination of Bevacizumab, Cetuximab, Cisplatin, and IMRT | Phase 2 clinical trial - | LA-HNSCC III/IVa/IVb | Exhibited good tolerability and anticancer activity. | [166] |
Dasatinib combined with EGFR inhibitor | Clinical trial - | HNSCC I–IV | Showed no clinical benefits. | [170] |
Phase II clinical trial - | R/M HNSCC - | Showed clinical relevance in patients with low serum IL-6 levels. | [171] | |
Combination of anti-IGF1R with Cetuximab | Phase 2 clinical trial - | R/M HNSCC - | Exhibited no significant improvement of OS and PFS. | [175] |
Combination of Paclitaxel and Cetuximab | Preclinical trial | N/A | Exerted synergistic effects, increasing anticancer response. | [176] |
Phase 2 clinical trial 1st line | R/M HNSCC - | Exhibited antitumoral activity and good tolerability. | [191] | |
Combination of Tipifarnib and Cetuximab | Preclinical trial | N/A | Enhanced cell inhibitory activity. | [179] |
Combination of Docetaxel and Trastuzumab | Phase 2 clinical trial Patients previously treated | SDC - | Showed an acceptable toxicity profile and promising efficacy for HER-2-positive SDC patients | [184] |
Afatinib combined with Docetaxel and postoperative radiation therapy | Phase 1 clinical trial - | LA-HNSCC II/III/IV | Exhibited high toxicity. | [185] |
Panitumumab in combination with Paclitaxel | Phase 2 clinical trial Patients previously treated | R/M HNSCC - | Exhibited good anticancer activity and was considered safe. | [186] |
Panitumumab combined with Paclitaxel followed by radiotherapy and Panitumumab | Phase 2 clinical trial 1st line (IC) | LA-HNSCC III/IVa/IVb | Toxicity worse than expected; however, led to a higher ORR. | [187] |
Cetuximab combined with a platinum and 5-FU | Phase 3 clinical trial 1st line | R/M HNSCC - | Displayed good anticancer response in OSCC patients, improving OS. | [188] |
Combination of Cetuximab with TPF | Phase 2 clinical trial 1st line (IC) | LA OCSCC IV | Exhibited a high ORR, was well tolerated and effective; however, no significant improvement of OS was observed. | [189] |
Combination of Cetuximab, Paclitaxel, and Carboplatin | Phase 2 clinical trial 1st line | R/M HNSCC III/IV | Showed good anticancer activity with acceptable toxicity. | [192] |
Phase 2 clinical trial 1st line (IC) | LA-HNSCC IVa/IVb | Good anticancer activity and promising survival was observed. | [193] | |
Combination of Cetuximab, Paclitaxel, and Cisplatin | Phase 2 clinical trial 1st line | R/M HNSCC - | Exhibited a moderate OS and low toxicity. | [194] |
Phase 2 clinical trial 1st line | R/M HNSCC - | No significant change in OS with the addition of Paclitaxel. | [195] | |
Phase 2b clinical trial 1st line | R/M HNSCC - | Addition of Paclitaxel did not improve patient’s outcome. | [196] | |
Gefitinib combined with Cisplatin | Preclinical trial | N/A | Exacerbated in vitro anticancer activity. | [197] |
Combination of Cetuximab, Docetaxel, and Cisplatin | Phase 2 clinical trial 1st line | R/M HNSCC - | Exhibited no significant improvement of OS when compared to EXTREME regime. However, can be an alternative in first-line treatment. | [198] |
Methotrexate combined with Cetuximab | Phase 1b/2 clinical trial 1st line | R/M HNSCC - | Improved PFS and clinical efficacy. | [199] |
Retrospective study ≥1st line | R/M HNSCC - | The treatment was deemed safe and is an option for palliative treatment. | [200] | |
Concurrent radiotherapy, Dacomitinib, and Cisplatin | Phase 1 clinical trial - | LA-HNSCC III/IVa/IVb | Tolerable side effects, but the study was early terminated since other studies showed high toxicity profiles and no improvement in the outcomes. | [201] |
Vandetanib combined with Cisplatin and radiotherapy | Phase 1 clinical trial 1st line | LA-HNSCC III/IV | Well tolerated. | [202] |
Combination of Nimotuzumab with Cisplatin and radiotherapy | Phase 3 clinical trial - | LA-HNSCC III/IV | Improved PFS and DFS. | [203] |
Phase 2 clinical trial 1st line | LA-HNSCC III/IV | Exhibited good tolerability, with high response rates. | [115] | |
Addition of Ipilimumab to concurrent Cetuximab and radiotherapy | Phase 1 clinical trial 1st line | LA-HNSCC III/IVa/IVb | Well tolerated and showed clinical activity. However, it did not meet PFS endpoint. | [116] |
Combination of histone deacetylase inhibitor with radiotherapy and EGFR or HER-2 inhibitors | Phase 1 clinical trial - | LA-HNSCC III/IV | Exhibited good tolerability at biologically effective doses. | [206] |
3.3. Cyclin-Dependent Kinase Inhibition-Based Combination Therapies
3.4. Bromodomain and Extra-Terminal Domain (BET) Proteins Inhibition-Based Combination Therapies
3.5. PD-1 and PD-L1 Inhibition-Based Combination Therapies
Combination Therapies | Study Design/Treatment Type | Cancer Type and Stage | Main Reported Outcome | References |
---|---|---|---|---|
Sitravatinib combined with Nivolumab | Clinical trial Preoperative | LA-HNSCC III/IVa | Exerted synergistic/addictive effects, promoting tumor reduction, and showed good safety. | [244] |
Combination of PD-1 and B7-H3 inhibitors | Phase 1/2 clinical trial - | R/M HNSCC - | Showed good tolerance, acceptable safety profile, and antitumoral activity. | [245] |
Combination of PD-1 and CTLA-4 inhibitors | Phase 2 clinical trial - | LA-OCSCC II/III/IVa | Exhibited high pathologic response and good safety profile. | [247] |
Phase 3 clinical trial 1st line | R/M HNSCC - | Better toxicity profile than the EXTREME regimen, but did not meet endpoint of OS. | [248] | |
Phase 3 clinical trial 1st line | R/M HNSCC - | Did not improve OS in patients with high expression of PD-L1. Led to lower median PFS, but with less grade 3/4 adverse events. | [249] | |
Phase 3 clinical trial 2nd line | R/M HNSCC - | Showed no significant improvement of OS comparing to standard therapies. | [250] | |
VEGFR inhibitors with anti-PD-1 mAbs | Phase 1 clinical trial Neoadjuvant | LA-OSCC III/IVa | Well tolerated and showed a major pathological response rate of 40% | [257] |
Phase 1b/2 clinical trial ≥1st line | R/M HNSCC - | Deemed tolerable and displayed promising anticancer activity. | [258] | |
Nivolumab in combination with Tadalafil | Clinical trial Neoadjuvant | HNSCC - | The treatment was safe, with 50% of the patients showing pathological treatment response. | [263] |
Pembrolizumab plus Acalabrutinib | Phase 2 clinical trial - | R/M HNSCC - | Showed no clinical benefit with high toxicity. | [252] |
Pembrolizumab combined with SD-101 | Phase 2 clinical trial ≥1st line | R/M HNSCC - | Overall, 24% of the patients showed objective response but did not reach the threshold. | [254] |
Combination of Nivolumab and Lirilumab | Phase 2 clinical trial Neoadjuvant/ adjuvant | LRR HNSCC I–IV | Led to high 2-year OS and a pathological response rate of 43%. | [256] |
Pembrolizumab plus Docetaxel | Phase 1/2 clinical trial ≥1st line | R/M HNSCC - | Achieved a median PFS of 5.8 months and a median OS of 21.3 with manageable toxicity. | [264] |
Camrelizumab, Paclitaxel or Docetaxel and Cisplatin | Phase 2 clinical trial Neoadjuvant | LA-HNSCC III/IVa/IVb | Led to high ORR and was well tolerated. | [265] |
TPF combined with an anti-PD-1 | Clinical trial 1st (IC) | LA-HNSCC III/IV | Displayed greater ORR and PFS than monotherapies, with no significant increase in adverse effects; however, no improvement of OS was observed. | [266] |
Addition of Toripalimab to Gemcitabine and Cisplatin | Phase 1b clinical trial Neoadjuvant | LA-HNSCC III/IVa/IVb | The therapy was considered safe and led to an increase in CD20 expression. | [267] |
Combination of Pembrolizumab with a platinum and 5-FU | Phase 3 clinical trial 1st line | R/M HNSCC - | Appropriate first-line treatment for R/M HNSCC. Four-year follow up showed continued survival benefit. | [28,268] |
Addition of Avelumab to standard-of-care chemoradiotherapy | Phase 3 clinical trial - | LA-HNSCC III/IVa/IVb | The objective of prolonging PFS was not achieved. | [269] |
Avelumab combined with Cetuximab and radiotherapy | Phase 2 clinical trial - | LA-HNSCC III/IV | Deemed tolerable. Improved PFS, but did not meet the endpoint | [270] |
Nivolumab in combination with Cetuximab | Phase 2 clinical trial Patients previously treated and untreated | R/M HNSCC - | Demonstrated manageable toxicity, with promising anticancer activity for both previously treated and untreated patients. | [271] |
Combination of Avelumab, Cetuximab, and Palbociclib | Phase 1 clinical trial 1st line | R/M HNSCC - | Showed good tolerability and clinical responses. | [272] |
Combination of Cetuximab and Pembrolizumab | Phase 2 clinical trial ≥1st line | R/M HNSCC - | Improved ORR and slightly increased toxicity when compared to single-drug therapies. | [273] |
Afatinib in combination with Pembrolizumab | Phase 2 clinical trial ≥1st line | R/M HNSCC - | The combination improved ORR. | [274] |
Cetuximab combined with Nivolumab | Phase 1/2 clinical trial 2nd line | R/M HNSCC - | Exhibited good safety; however, no improvement of OS was observed. | [275] |
Combination of Vorinostat and Pembrolizumab | Phase 2 clinical trial - | R/M HNSCC and SGC - | Exerted synergistic effects, increasing anticancer activity. Higher toxicity than Pembrolizumab monotherapy. | [276] |
Resveratrol combined with PD-L1 Inhibition | Preclinical trial | N/A | Exhibited in vitro and in vivo antiproliferative effects. | [277] |
Atezolizumab plus Cobimetinib | Phase 2 clinical trial - | HNSCC - | Moderate activity was observed for patients who had not previously been treated with PD-1/PD-L1 inhibitors. | [281] |
Navoximod combined with Atezolizumab | Phase 1 clinical trial - | HNSCC - | Showed acceptable safety and tolerability profile and antitumoral activity, but there was no evidence of a benefit of the combination. | [284] |
Epacadostat combined with Pembrolizumab | Phase 1/2 clinical trial - | HNSCC - | Exhibited good safety and moderate anticancer response. | [285] |
3.6. Microtubule Inhibition-Based Combination Therapies
Combination Therapies | Study Design/Treatment Type | Cancer Type and Stage | Main Reported Outcome | References |
---|---|---|---|---|
Combination of Buparlisib and Paclitaxel | Phase 2 clinical trial 2nd line | R/M HNSCC - | Increased PFS, OS, and ORR when compared to single paclitaxel therapy; however, higher toxicity was observed. | [292] |
Combination of Docetaxel and PX-866 | Phase 2 clinical trial 2nd and 3rd line | R/M HNSCC - | Exerted no improvement in PFS, ORR, or OS when compared to docetaxel monotherapy. | [293] |
Gemcitabine combined with Paclitaxel | Phase 2 clinical trial 1st line | R/M HNSCC - | Exhibited satisfactory efficacy and good safety, with no treatment related deaths. | [294] |
Combination of Cisplatin with Genexol-PM | Phase 2 clinical trial 1st line (IC) | LA-HNSCC III/IVa/IVb | Promoted tumor reduction in 48 of the 52 patients | [296] |
Combination of Temsirolimus with low-dose weekly Carboplatin and Paclitaxel | Phase 2 clinical trial ≥1st line | R/M HNSCC - | Exerted synergistic effects, with manageable toxicity profile. | [297] |
Combination of Docetaxel, Cetuximab, 5-FU, and Cisplatin | Phase 2 clinical trial 1st line | R/M HNSCC - | Did not improve efficacy and showed high toxicity profile and mortality rate. | [298] |
AZD1775 combined with Cisplatin, Gemcitabine, or Carboplatin | Phase 1 clinical trial - | HNSCC - | Exhibited good tolerability in patients with advanced solid tumors. | [300] |
AZD1775 combined with neoadjuvant weekly Docetaxel and Cisplatin | Phase 1 clinical trial - | LA-HNSCC III/IVb | Exhibited a good safety, efficiency, and tolerability profile. | [299] |
Combination of WEE1 and PARP inhibitors | Preclinical trial | N/A | Exerted no synergistic effects | [224] |
3.7. Other Target Inhibition-Based Combination Therapies
Combination Therapies | Study Design/Treatment Type | Cancer Type and Stage | Main Reported Outcome | References |
---|---|---|---|---|
Combination of α-Mangostin with TRAIL treatment | Preclinical trial | N/A | Inhibited cell proliferation and promoted tumor apoptosis in OSCC. | [304] |
Solid lipid nanoparticles containing Paclitaxel and AA | Preclinical trial | N/A | Exerted high efficacy, leading to moderate dysplasia in vivo. | [9] |
Combination of heteronemin with tetrac | Preclinical trial | N/A | Exerted synergistic effects potentiating anticancer activity. | [10] |
Navitoclax combined with NOXA inducer | Preclinical trial | N/A | Efficiently promoted HNSCC cell death by apoptosis. | [314] |
Navitoclax combined with MCL-1 inhibitor | Preclinical trial | N/A | The combination exhibited synergistic activity. | [318] |
Combination of PI3K and autophagy inhibitors | Preclinical trial | N/A | Exerted synergistic effects, decreasing cancer cells proliferation. | [321] |
Combination of an anti-IGF1R with an Src inhibitor | Preclinical trial | N/A | Exerted synergistic effects, enhancing anticancer response in HNSCC cells. | [322] |
Nanoparticle albumin-bound Paclitaxel combined with Cetuximab and Carboplatin | Phase 2 clinical trial 1st line | R/M HNSCC - | Improved ORR and OS and induced tumor reduction; however, no improvement in PFS was observed. | [323] |
Irinotecan combined with Bortezomib | Phase 2 clinical trial - | LA-HNSCC - | Reduced OS when compare with other therapies. | [326] |
Combination of Ridaforolimus and MK-0752 | Phase 1 clinical trial - | R/M HNSCC - | Showed activity in HNSCC patients, but considerably increased the side effects in patients with advanced solid tumors. | [327] |
Combination of Motolimod with the EXTREME regimen | Phase 2 clinical trial 1st line | R/M HNSCC - | Exerted good safety; however, no improvements of PFS and OS in HNSCC patients were observed. Led to enhanced outcomes for HPV-positive oropharyngeal cancer patients. | [330] |
Combination of LSD1 and YAP inhibition | Preclinical trail | N/A | Exerted additive effects in inhibiting cell proliferation. | [334] |
Combination of HIF-1α and Trx-1 inhibitor | Preclinical trail | N/A | Exerted synergistic effect under hypoxia condition and addictive effects in normoxia. | [335] |
4. Conclusions and Future Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Combination Therapies | Study Design/Treatment Type | Cancer Type and Stage | Main Reported Outcome | References |
---|---|---|---|---|
Palbociclib combined with Afatinib | Preclinical trial | N/A | Induced cellular senescence and inhibited tumor growth. | [208] |
Combination of Cetuximab with Ribociclib or Palbociclib | Preclinical trial | N/A | Exhibited less effectiveness than Ribociclib monotherapy in Cetuximab-resistant PDTX models. No improvement in anticancer response was observed when compared with Cetuximab alone. | [213] |
Phase 1 clinical trial - | R/M HNSCC - | Displayed good anticancer response, with tolerable side effects. | [214,215] | |
Phase 2 clinical trial - | R/M HNSCC I–IV | Exhibited no significant improvement of OS and higher side effects than Cetuximab single therapy. | [216] | |
Palbociclib combined with Cetuximab | Phase 2 clinical trial Patients previously treated | R/M OPSCC - | Did not meet primary endpoint. | [217] |
The combination of a CDK4/6 inhibitor with Suberanilohydroxamic acid | Preclinical trial | N/A | Enhanced inhibition of NPC cell growth in vitro and in vivo. | [218] |
Palbociclib combined with Cisplatin | Preclinical trial | N/A | Exerted antagonistic effects, reducing cancer cell cytotoxicity. | [218] |
Addition of Pablociclib and Carboplatin | Phase 2 clinical trial - | R/M HNSCC - | Insufficient antitumoral activity and high toxicity. | [220] |
Combination of JQ1 with Palbociclib | Preclinical trial | N/A | Exerted synergistic effects, reducing tumor volume in vivo. | [221] |
PI3K inhibitor combined with Palbociclib | Preclinical trial | N/A | Exhibited in vitro and in vivo controlled tumor growth. | [223] |
Palbociclib combined with Dinaciclib | Preclinical trial | N/A | Exerted synergistic effects in tongue squamous cell carcinoma. | [207] |
Dinaciclib combined with Cisplatin | Preclinical trial | N/A | Increased tumor growth inhibition in vivo. | [207] |
Combination Therapies | Study Design | Main Reported Outcome | References |
---|---|---|---|
JQ1 combined with PI3K inhibitor | Preclinical trial | Exerted synergistic effects, increasing treatment efficacy in vivo and in vitro. | [228] |
Combination of BRD4 and CDK7 inhibitors | Preclinical trial | Exhibited in vitro and in vivo synergistic effects. | [235] |
Combination of a YAP inhibitor with melatonin | Preclinical trial | Exerted synergistic effects, increasing apoptosis and reducing metastatic activity. | [237] |
JQ1 combined with siPD-L1 | Preclinical trial | Improved in vitro and in vivo tumor growth inhibition. | [239] |
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Silva, J.P.N.; Pinto, B.; Monteiro, L.; Silva, P.M.A.; Bousbaa, H. Combination Therapy as a Promising Way to Fight Oral Cancer. Pharmaceutics 2023, 15, 1653. https://doi.org/10.3390/pharmaceutics15061653
Silva JPN, Pinto B, Monteiro L, Silva PMA, Bousbaa H. Combination Therapy as a Promising Way to Fight Oral Cancer. Pharmaceutics. 2023; 15(6):1653. https://doi.org/10.3390/pharmaceutics15061653
Chicago/Turabian StyleSilva, João P. N., Bárbara Pinto, Luís Monteiro, Patrícia M. A. Silva, and Hassan Bousbaa. 2023. "Combination Therapy as a Promising Way to Fight Oral Cancer" Pharmaceutics 15, no. 6: 1653. https://doi.org/10.3390/pharmaceutics15061653
APA StyleSilva, J. P. N., Pinto, B., Monteiro, L., Silva, P. M. A., & Bousbaa, H. (2023). Combination Therapy as a Promising Way to Fight Oral Cancer. Pharmaceutics, 15(6), 1653. https://doi.org/10.3390/pharmaceutics15061653