NcXHF

TARGETED THERAPY IN MELANOMA
variety of different solid tumor types and clinical indications,
in addition to opening the possibility of regular monitoring
of patients and changing treatments as necessary. 108 However,
even if clinically relevant biomarkers and actionable
mutations are discovered, there may not be a matched agent
in development that effectively targets them.
The use of novel targeted combinations is also complicated
by the many different motivations of the various stakeholders
involved in drug development, including pharmaceutical
companies, academic researchers, and regulatory
agencies. 105,109,110 All too often, these stakeholders have different
priorities, such as intellectual property, conflict of interest,
incentives for academics, and publication policies.
Different views on these priorities can lead to distrust, a decision
not to collaborate, and eventual failure of a project.
Lack of collaboration can lead to duplication of efforts and
lack of progress, resulting in ineffıcient use of limited patient
and fınancial resources. 105 Finding a way to satisfy these different
priorities is critical in order to move therapies forward
in the most effıcient manner possible.
CONCLUSION
Although not without challenges, the use of novel targeted
therapies in the context of molecular testing has opened new
avenues for a precision medicine approach for metastatic
melanoma, including a signifıcant benefıt already realized for
this patient population. In some cases impressive tumor regressions
have been demonstrated (Table 1); however, responses
are not seen in the majority of patients with non-
BRAF mutated cancer who are treated with targeted therapy
and relapse is frequent in such cases despite combination
therapy with BRAF and MEK inhibitors. Intensive translational
research has highlighted the complexity of the resistance
mechanisms involved and offers opportunities for
interventions and improved patient outcomes. There is a
need for additional clinical trials accompanied by highthroughput
biomarker analyses to further improve these outcomes.
Overcoming the scientifıc challenges, as well as
satisfying the priorities of the various stakeholders involved
in the development of novel therapies, will be critical for improving
the treatment of patients with melanoma.
Disclosures of Potential Conflicts of Interest
Relationships are considered self-held and compensated unless otherwise noted. Relationships marked “L” indicate leadership positions. Relationships marked “I” are those held by an immediate
family member; those marked “B” are held by the author and an immediate family member. Institutional relationships are marked “Inst.” Relationships marked “U” are uncompensated.
Employment: None. Leadership Position: None. Stock or Other Ownership Interests: None. Honoraria: Reinhard Dummer, BMS, GSK, MSD, Novartis,
Roche. Consulting or Advisory Role: Reinhard Dummer, BMS, GSK, MSD, Novartis, Roche. Patricia LoRusso, Astex, Novartis, Astellas, Genentech. Ryan J.
Sullivan, Astex Therapeutics. Speakers’ Bureau: Patricia LoRusso, Genentech. Research Funding: Reinhard Dummer, BMS, GSK, MSD, Novartis, Roche.
Patricia LoRusso, Genentech (Inst), Novartis (Inst), Merrimack (Inst), Immunogen (Inst), Tensha (Inst), Tailho (Inst). Patents, Royalties, or Other
Intellectual Property: None. Expert Testimony: None. Travel, Accommodations, Expenses: None. Other Relationships: None.
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