Inclusion Criteria:
1. Participants must have developed either a grade 2, 3, or 4 rash categorized as acneiform while taking tumor-directed therapy that targets the MAPK pathway.
* Acneiform rash will be defined according to CTCAE v5.0 as a disorder characterized by an eruption of papules and pustules, typically appearing in face, scalp, upper chest and back.
1. Grade 2 = Papules and/or pustules covering 10-30% body surface area (BSA), which may or may not be associated with symptoms or of pruritus or tenderness; associated with psychosocial impact; limiting instrumental Activities of Daily Living (ADL); papules and/or pustules covering \> 30% BSA with or without mild symptoms.
2. Grade 3 = Papules and/or pustules covering \> 30% BSA with moderate or severe symptoms; limiting self-care ADL; associated with local superinfection with oral antibiotics indicated.
3. Grade 4 = Life-threatening consequences; papules and/or pustules covering any % BSA, which may or may not be associated with symptoms of pruritus or tenderness and are associated with extensive superinfection with IV antibiotics indicated.
2. Prior Therapy: Participants may have received either doxycycline or isotretinoin in the past for treatment of their targeted therapy induced rash or acne. However, if they took doxycycline or another tetracycline antibiotic for a rash caused by a targeted therapy or for acne, the last dose must have been at least 4 weeks before study registration. If a participant took isotretinoin for any reason, the last dose must be at least 6 months prior to study registration.
3. Age. 12-39 years old.
4. Organ Function Requirements.
a. Adequate Liver Function Defined as:
* Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \< 3 x ULN or direct bilirubin \< 1.5 x ULN
* alanine aminotransferase (ALT) ≤ 3 x ULN
* aspartate aminotransferase (AST) ≤ 3 x ULN.
* Serum triglycerides \< 500 mg/dL or \< 5.7 mmol/L
5. Due to the harmful effects of isotretinoin and doxycycline on the developing human fetus women of child-bearing potential and men must agree to use adequate contraception (as recommended by the iPLEDGE system if residing in the United States for those who will take isotretinoin) prior to study entry, for the duration of study participation, and one (1) month after completion of isotretinoin and doxycycline administration. If a participant requires contraception, they will require two forms of contraception as outlined by the iPLEDGE system. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. The proper steps in the iPLEDGE system must also be taken.
6. Participants must be able and willing to take a gelatin capsule.
7. Participants must be able to swallow pills.
8. A legal parent/guardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate.
Exclusion Criteria:
1. History of allergic reactions attributed to compounds of similar chemical or biologic composition to doxycycline or isotretinoin, or other agents used in study. Participants also must not have a paraben allergy.
2. Participants taking any medications listed must be discussed with study chair(s).
3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, other than skin infection in setting of rash.
4. Women of childbearing potential must not be pregnant or breast-feeding.
5. Participants who report active suicidal ideation due to isotretinoin's black box warning.
6. Participants who refuse to be photographed for the centralized dermatology review.
