Cancer Treatment
Types

Cancer Treatment Types

This list includes many therapeutic options approved in select solid tumor types. Additional drug targets are under investigation across all cancer types.

Chemotherapy

Chemotherapy-based regimens are preferred therapeutic options for many solid tumors in both the neoadjuvant and adjuvant settings.¹ Generally, chemotherapies target the proliferative nature of cancer cells, as in the case of taxanes, which inhibit microtubule depolymerization, triggering mitotic arrest and ultimately cell apoptosis.² Because chemotherapies cause tissue cytotoxicity, nano-drug strategies that focus on tumor targeting and safety tolerance remain ongoing areas of research and development.²

Hormone Therapies

Aromatase Inhibitors

Aromatase inhibitors inhibit the aromatase enzyme, which catalyzes the last step of estrogen conversion from androgen precursors such as testosterone.^3,4 Neoadjuvant endocrine monotherapy may be offered to patients with strongly hormone receptor–positive tumors.¹ Aromatase inhibitors are the preferred therapeutic option for postmenopausal patients with breast cancer.¹ Aromatase inhibitors are also options for premenopausal patients when they are combined with ovarian suppression therapy or tamoxifen.¹ Recent literature has divided aromatase inhibitors into steroidal and nonsteroidal subgroups (SAIs and NSAIs, respectively).⁴ SAIs bind covalently and irreversibly to aromatase, resulting in major androgenic side effects such as infertility and osteoporosis. NSAIs, on the other hand, are reversible and bind noncovalently to aromatase, resulting in fewer adverse events.⁴

Selective Estrogen Receptor Modifiers/Degraders

Estrogen receptor alpha (ERα) is targeted directly by selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs).³ SERMs compete with estrogen for ER binding, whereas SERDs create an unstable ER protein complex that results in degradation via the proteasome.³ SERDs are preferred options for first-line treatment in combination with NSAIs.¹ In later lines, SERMs in combination with an mTOR kinase inhibitor are among the preferred options.¹ Although hormone therapy has significantly reduced recurrence and mortality among patients with breast cancer, resistance remains a major challenge.³

Immunotherapy

Immune checkpoint inhibitors (ICIs) activate T cells, thereby producing a robust activation of the innate and adaptive immune systems.⁵ These immune responses are observed within tumors and in peripheral organs such as the draining lymph nodes and peripheral blood.⁵ As of 2021, ICIs had been developed for the following 3 targets: T-lymphocyte–associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), and the programmed cell death ligand 1 (PD-L1).^5-7

Targeted Therapies

Antibody-Drug Conjugates

Antibody-drug conjugates (ADCs) harness the specificity of monoclonal antibodies to deliver cytotoxic agents directly to tumor cells, sparing healthy cells and reducing the occurrence of side effects commonly associated with traditional chemotherapy regimens.⁸ A chemical linker connecting the antibody to the cytotoxic drug (or payload) is cleaved or degraded upon internalization of the conjugate by the tumor cell, releasing the payload to induce apoptosis.^9,10 Neighboring tumor cells may also be killed in a “bystander” effect, expanding payload targeting in conditions of low target antigen expression or heterogeneous tumor cell types.¹¹ ADCs currently approved by the FDA may be used in neoadjuvant and adjuvant settings (depending on the indication) for solid tumors and target HER2-, Nectin-4–, and Trop-2–expressing tumor cells.^10,12 The efficacy of ADCs requires presence of the target antigen and careful patient selection; however, cancerous cells may develop resistance to ADCs via numerous poorly characterized mechanisms.^10,13 The identification of new antibody targets, development of cytotoxic drugs and optimization of their potency, and investigation of mechanisms of resistance are ongoing areas of research to improve the efficacy of ADCs.^10,13

BRAF/MEK Inhibitors

Mutations in the BRAF gene can lead to overactivation of BRAF kinase, an important component of the mitogen-activated protein kinase (MAPK) signaling cascade that regulates cellular proliferation, migration, growth, differentiation, and survival.¹⁴ Mutations of BRAF have a high frequency in many cancer types (eg, melanoma, thyroid tumors, and type I ovarian cancer), with the BRAF V600E mutation being the most clinically relevant.^14,15 BRAF inhibitors competitively bind BRAF kinase to interfere with the aberrant MAPK signaling that promotes proliferation and survival of cancer cells; however, many patients develop resistance to adjuvant BRAF inhibitor monotherapy.^15,16 Because inhibition of MAPK kinase (MEK) interferes with MAPK signaling downstream of BRAF kinase, MEK inhibitors may be used to augment BRAF inhibitors in adjuvant combination therapy in patients who have melanoma and thyroid cancers with the BRAF V600E mutation.^15-17

CDK4/6 Inhibitors

Inhibition of CDK4/6 provides selective reduction of cell proliferation by arresting upregulated cell cycle progression in tumor cells.¹⁸ CDK4/6 inhibitors are currently recommended as first-line therapy in combination with endocrine therapy for patients with hormone-responsive, HER2- advanced metastatic breast cancer.¹ Subsequent work investigating prolonged adjuvant CDK4/6 inhibition in early breast cancer demonstrated no benefit compared with endocrine therapy alone.¹⁹ However, research is ongoing regarding the efficacy of currently approved CDK4/6 inhibitors in combination therapy for other cancer types.²⁰

Tyrosine Kinase Inhibitors

Excessive activation of tyrosine kinase receptors contributes to tumor survival, proliferation, and angiogenesis.²¹ Therefore, tyrosine kinase inhibitors (TKIs) can regulate cancer growth by blocking cell growth, migration, differentiation, and more.²² TKIs bind tyrosine kinase receptors to prevent their activation.²³ With up to 20 different families of tyrosine kinase receptors, TKIs have a large variety of targets, including receptors for EGF, VEGF, RET, ROS1, ALK, MET, GDNF, PDGF, and FGFR.^21-25 Given the breadth of possible TKI targets, tumor genotyping may be advisable to identify the most effective treatment on a case-by-case basis.^23,25,26 Although the selectivity with TKI therapeutics is continuously being improved,^23,25,26 treatment with TKIs may result in a variety of off-target adverse effects.²²

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.4.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed November 16, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way. 2. Chen et al. Am J Cancer Res. 2021;11:3445-3460. 3. Hernando et al. Int J Mol Sci. 2021;22:7812. 4. Kharb et al. Arch Pharm. 2020;353:e2000081. 5. Bagchi et al. Annu Rev Pathol. 2021;16:223-249. 6. Burton et al. Neurooncology Adv. 2021;3:v108-v120. 7. Vafaei et al. Cancer Cell Int. 2022;22:2. 8. Baah et al. Molecules. 2021;26:2943. 9. Thomas et al. Lancet Oncol. 2016:17:e254-e262. 10. Fu et al. Signal Transduct Target Ther. 2022;7:93. 11. Staudacher and Brown. Br J Cancer. 2017;117:1736-1742. 12. Criscitiello et al. J Hematol Oncol. 2021;14:20. 13. Makawita and Meric-Bernstam. Am Soc Clin Oncol Educ Book. 2020;40:1-10. 14. Crispo et al. Cancers (Basel). 2019;11:1388. 15. Proietti et al. Cancers (Basel). 2020;12:1823. 16. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Melanoma: Cutaneous V.3.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed November 16, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way. 17. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Thyroid Carcinoma V.2.2022. © National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed November 16, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way. 18. Hamilton and Infante. Cancer Treat Rev. 2016;45:129-138. 19. Loibl et al. J Clin Oncol. 2021;39:1518-1530. 20. Yuan et al. Acta Pharm Sin B. 2021;11:30-54. 21. Illouz et al. Eur J Endocrinol. 2009;160:331-336. 22. Thomson et al. https://www.ncbi.nlm.nih.gov/books/NBK563322/?report=printable. Accessed March 28, 2022. 23. Esteban-Villarrubia et al. Int J Mol Sci. 2020;21:8529. 24. Huang et al. J Hematol Oncol. 2020;13:143. 25. Levine et al. Pharmacol Ther. 2020;214:107590. 26. Yen et al. Int J Gynecol Pathol. 2020;39:26-35.